PF-04217903 phosphate
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PF-04217903 phosphate is an orally active, highly selective ATP-competitive c-Met kinase inhibitor with a Ki value of 4.8 nM and a Kd value of 4.5 nM. PF-04217903 phosphate blocks c-Met and HGF signaling pathways, inhibits MET phosphorylation, and blocks downstream MAPK, PI3K/AKT and PLCγ1 pathways. PF-04217903 phosphate suppresses tumor proliferation, survival, migration, invasion, angiogenesis and metastasis, induces apoptosis, and enhances efferocytosis, Annexin A1 expression and resolution of inflammation. PF-04217903 phosphate retains activity against several c-Met mutants (M1131T, V1220I, H1094R). PF-04217903 phosphate increases the incidence of subarachnoid hemorrhage and reduces survival rate without altering aneurysm formation, and also prevents lymph node metastasis induced by VEGF inhibition. PF-04217903 phosphate is applicable to research related to tumors (pancreas, stomach, lung, brain, colon, breast, kidney, melanoma, etc.), intracranial aneurysms and inflammatory diseases (gouty arthritis, neutrophilic pleuritis).
For research use only. We do not sell to patients.
- CAS No.: 1159490-83-1
- Formula: C19H19N8O5P
- Molecular Weight:470.38
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Biological Activity
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c-Met 4.8 nM (Ki) |
c-Met 4.5 nM (Kd) |
PLC |
AnxA1 |
PF-04217903 phosphate is a highly selective c-Met inhibitor, with a potency against c-Met that is over 1000-fold higher than its potency against the other 208 tested kinases[1][9].
PF-04217903 (1 μM) phosphate exerts biochemical inhibitory effects on IGF1R in kinase selectivity screening, but does not inhibit IGF1R activity in cell-based assays[8].
PF-04217903 (30 min) phosphate potently inhibits wild-type c-Met (Ki = 6.5-7.4 pM) and most oncogenic c-Met mutants, but shows significantly reduced potency against c-MetY1230C, c-MetY1230H and c-MetD1228H mutants, with no detectable inhibitory activity against c-MetD1228H[9].
PF-04217903 (80 min) potently inhibits c-Met phosphorylation in cells expressing wild-type or most mutant forms of c-Met (IC50 = 3.1-24 nM), but shows no detectable inhibitory effect in NIH-3T3 cells expressing the c-MetY1230C mutant (IC50 >10000 nM), and exhibits significantly reduced activity in T47D cells expressing the c-MetY1235D mutant[9].
PF-04217903 phosphate (7.8-1000 nM; 1 min association, 5 min dissociation) binds tightly to the purified c-Met kinase domain, with a Kd value of 4.5 nM and a residence time of 180 s[9].
PF-04217903 (5 μM; 30 min) phosphate significantly stabilizes wild-type c-Met and most oncogenic c-Met mutants (Tm shift = 11.6-17.0 °C), but shows extremely weak stabilizing effects on the c-MetY1230C (Tm shift = 2.1 °C) and c-MetY1230H (Tm shift = 4.4 °C) mutants[9].
PF-04217903 (6 μg/mL; 1 hour pre-incubation, followed by 3 hours of LPS (HY-D1056A1) treatment) phosphate blocks HGF-mediated downregulation of VCAM-1 and E-selectin expression in human aortic endothelial cells, but exerts no effect on the expression of inflammatory molecules in human aortic smooth muscle cells or THP-1 monocytes[3].
PF-04217903 (6 days) phosphate potently inhibits the growth of Met-amplified recurrent mouse ATC cell lines 34286 (IC50 ~150 nM) and 36934 (IC50 ~50 nM), but exhibits only very low activity against primary mouse ATC cell lines and Met-diploid recurrent mouse ATC cell lines[4].
PF-04217903 (10-1000 nM; 1 hour) inhibits Met phosphorylation and the downstream Akt/Erk signaling pathway in Met-amplified recurrent mouse ATC cell lines, but exerts no effect on these signaling pathways in primary mouse ATC cell lines or Met-diploid recurrent mouse ATC cell lines[4].
PF-04217903 phosphate (153 pM-10 μM; 3 days) inhibits the viability of parental GTL16 gastric cancer cells with an IC50 of 10 nM, but shows no inhibitory effect on the viability of drug-resistant GTL16R1 and GTL16R3 clones harboring the SND1-BRAF fusion mutation even at concentrations as high as 10 μM[8].
PF-04217903 (2.5 μM; 1 h) phosphate inhibits the phosphorylation of c-MetY1235 in parental GTL16, GTL16R1 and GTL16R3 gastric cancer cells, confirming that this inhibitor binds to c-Met in drug-resistant clones and inhibits its catalytic activity[8].
PF-04217903 (200 nM; 4 h) phosphate inhibits the phosphorylation of c-Met Y1349 and AKT S473 in parental GTL16, GTL16R1 and GTL16R3 gastric cancer cells; it completely blocks ERK phosphorylation in parental GTL16 cells, but only partially reduces ERK phosphorylation in drug-resistant clones, whereas combination treatment with RAFi achieves stronger ERK inhibition in drug-resistant clones[8].
PF-04217903 phosphate (40 pM-10 nM; 3 days) acts synergistically with the RAF inhibitor PF-04880594 (HY-13810) or the MEK inhibitor PD-0325901 (HY-10254) to inhibit the cell viability of SND1-BRAF fusion-positive drug-resistant gastric cancer clones GTL16R1 and GTL16R3[8].
PF-04217903 phosphate (0.5-2.5 μM; 4 months) generates PF-04217903-resistant cell clones from GTL16 gastric cancer cells[8].
PF-04217903 (30 µM; 1-6 h) phosphate inhibits MET phosphorylation in human primary peripheral blood neutrophils induced by LPS/HGF and MSU, and induces caspase-dependent apoptosis by increasing the level of activated caspase-3 and decreasing the level of Bcl-xL[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human aortic endothelial cells, human aortic smooth muscle cells, THP-1 human monocyte cells
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Concentration:6 μg/mL
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Incubation Time:1 h (pre-incubation); 3 hs (LPS treatment)
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Result:Abolished the HGF-mediated attenuation of VCAM-1 and E-selectin expression induced by LPS in human aortic endothelial cells, such that VCAM-1 and E-selectin levels were similar to those in cells treated with LPS alone.
Showed no significant effects on TNF-α, IL-1β, MCP-1, COX-1, COX-2, TGF-β, or ICAM-1 expression in human aortic endothelial cells.
Had no significant effect on any measured inflammatory molecule expression in human aortic smooth muscle cells and THP-1 monocytes when combined with HGF and LPS, compared to LPS alone or HGF plus LPS.
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Cell Line:murine primary ATCs and Met-amplified/Met-diploid recurrent murine ATCs
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Concentration:10, 50, 200 and 1000 nM
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Incubation Time:1 h
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Result:Inhibited phosphorylation of Met (Y1234/Y1235) only in Met-amplified recurrent ATC cell lines 34286 and 36934, with reduced pMet visible at doses as low as 10 nM.
Blocked downstream phosphorylation of Akt (S473) and Erk (T202/Y204) in these Met-amplified lines, but had no effect on pMet, pAkt, or pErk levels in primary ATC or Met-diploid recurrent ATC cell lines.
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Cell Line:Primary human peripheral blood neutrophils
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Concentration:30 µM
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Incubation Time:1, 2 and 6 h
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Result:Selective HGF/MET inhibition blocked MET phosphorylation in human primary neutrophils stimulated by LPS/HGF or MSU crystals.
MET blockade increased neutrophil apoptosis at 6 hours, evidenced by chromatin condensation and nuclear fragmentation.
This apoptosis was caspase-dependent, as zVAD-fmk abolished the effect at 2 hours.
Mechanistically, MET suppression elevated cleaved caspase-3 and reduced Bcl-xL expression.
The effect was neutrophil-specific, as MET inhibition did not induce macrophage apoptosis in vivo.
Additionally, MET blockade reversed the pro-survival effect of combined LPS/HGF stimulation.
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Cell Line:parental GTL16 gastric carcinoma cells, METi-resistant GTL16R1, GTL16R3 clones
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Concentration:200 nM (single agent); 2.5 μM (combination treatment assays)
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Incubation Time:4 h (single agent)
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Result:Inhibited phosphorylation of c-Met Y1349 in all three cell lines, despite moderately increased total c-Met protein levels in treated samples.
Completely inhibited ERK phosphorylation in parental GTL16 cells, but only caused a slight decrease in ERK phosphorylation in GTL16R1 and GTL16R3 clones.
Reduced AKT S473 phosphorylation to ~10% of baseline levels in all cell lines.
When combined with 200 nM RAFi, further inhibited ERK phosphorylation in GTL16R1 and GTL16R3 to 38% and 10.5% of untreated GTL16 levels, respectively.
PF-04217903 (30 mg/kg; p.o.; once daily; for 3 consecutive weeks) phosphate enhances the anti-tumor growth and anti-invasion effects of Sunitinib (HY-10255A) in a nude mouse orthotopic Panc-1 pancreatic adenocarcinoma model, and eliminates the micrometastases observed with Sunitinib monotherapy[1].
PF-04217903 (30-45 mg/kg; p.o.; once daily administration) phosphate exerts potent and selective in vivo growth inhibitory effects on Met-amplified recurrent anaplastic thyroid carcinoma xenografts in nude mice[4].
PF-04217903 (40 mg/kg; p.o.; once daily; for 25 consecutive days) phosphate achieves a 45% tumor growth inhibition (TGI) rate in the c-Met-overexpressing SW620 xenograft model, while sustaining inhibition of c-Met phosphorylation and upregulating total c-Met protein expression after treatment[6].
PF-04217903 (40-50 mg/kg; p.o.; once daily; for 14-31 consecutive days) phosphate inhibits tumor growth in c-Met-overexpressing Colo205, MDA-MB-231, and H292 xenograft models[6].
PF-04217903 (10 mg/kg; p.o.; daily administration; for 21 consecutive days) phosphate does not alter intracranial aneurysm formation in a mouse model of intracranial aneurysm, but increases the incidence of subarachnoid hemorrhage to 94% and reduces the survival rate to 25%[3].
PF-04217903 (40 mg/kg; p.o.; single administration; 12 h after MSU challenge) phosphate induces caspase-dependent neutrophil apoptosis and efferocytosis, alleviates joint inflammation, tissue damage and hyperalgesia, and promotes the expression of the pro-resolving protein annexin A1 in a mouse model of MSU-induced gouty arthritis[5].
PF-04217903 (40 mg/kg; p.o.; single administration; 4 h after LPS challenge) phosphate promotes the resolution of inflammation in a mouse model of LPS (HY-D1056A1)-induced neutrophilic pleurisy by enhancing neutrophil apoptosis and efferocytosis[5].
PF-04217903 (40 mg/kg; p.o.; single administration; 90 h after Zymosan (HY-W250113) challenge) phosphate enhances the efferocytosis capacity of macrophages in a Zymosan-induced mouse model of peritonitis[5].
PF-04217903 (1-30 mg/kg; p.o.; once daily; 16 days; 0.15-15 mg/kg/d; s.c.; continuous infusion; 14 days; 0.3-10 mg/kg/d; p.o.; once daily; 4 days) phosphate exhibits potent, dose-dependent antitumor efficacy in MET-amplified GTL-16 xenograft models, with a tumor growth inhibition (TGI) rate of 100% at an oral dose of 30 mg/kg/d. Its antitumor activity directly correlates with sustained inhibition of c-Met phosphorylation and downstream signaling pathways, as well as induction of tumor cell apoptosis[6].
PF-04217903 (0.3-30 mg/kg; p.o.; once daily; for 10 consecutive days; 5-50 mg/kg; p.o.; once daily; for 3 consecutive days) phosphate exhibits dose-dependent antitumor efficacy in U87MG xenograft models with an HGF/c-Met autocrine loop, achieving a tumor growth inhibition (TGI) rate of 84% at an oral dose of 30 mg/kg/d. Its activity is mediated by inhibiting the c-Met signaling pathway, reducing tumor cell proliferation, inducing apoptosis, exerting anti-angiogenic effects, and decreasing the secretion of pro-angiogenic cytokines[6].
PF-04217903 (50 mg/kg; p.o.; once daily; for 21 consecutive days) phosphate achieves a tumor growth inhibition (TGI) rate of 40% as a monotherapy in c-Met-overexpressing HT29 xenograft models; the efficacy of combination therapy can be increased to a TGI rate of 77% due to the blockade of the AKT signaling pathway and the induction of tumor cell apoptosis[6].
PF-04217903 (1-30 mg/kg/d; p.o.; multiple administrations) phosphate dose-dependently reduces the plasma levels of pro-angiogenic factors IL-8 and VEGFA in mice bearing GTL-16 xenograft tumors[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6-Tg (RIP-Tag) 2Han mice (aged 14 weeks at treatment initiation, spontaneously developed pancreatic neuroendocrine tumors driven by RIP-promoter SV40 T antigen expression in β-cells)[1]
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Dosage:30 mg/kg (single-agent; co-administered with anti-mouse VEGF antibody; co-administered with Sunitinib) (HY-10255A); 150 μg (anti-mouse VEGF antibody); 40 mg/kg (sunitinib)
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Administration:p.o.; daily; 3 weeks; p.o.; daily; 6 weeks (survival study); i.p.; 3x/week; 3 weeks (anti-mouse VEGF antibody)
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Result:Reduced amylase-positive area density from ~4.8% to ~3.2%.
Reduced liver metastases 98% (from 0.7 to 0.014 per mm2), with mean diameter reduced 40% (from 90 to 54 μm).
Prolonged median survival to 16.1 weeks compared to 14.7 weeks for vehicle.
Reduced trapped acinar cell area density from ~12% to ~3% when co-administered with anti-VEGF antibody.
Reduced liver metastases 92% (from 3.5 to 0.28 per mm2), with mean diameter reduced 50% (from 172 to 86 μm) when co-administered with anti-VEGF antibody.
Achieved 70% survival rate over 3 weeks (vs. 50% for anti-VEGF antibody alone) when co-administered with anti-VEGF antibody.
Prolonged median survival to 17.3 weeks in the 6-week study when co-administered with anti-VEGF antibody.
Reduced trapped acinar cell area density by 38% (from ~9% to ~3.0%) when co-administered with Sunitinib (HY-10255A).
Reduced liver metastases 99% (from 1.3 to 0.013 per mm2), with mean diameter reduced 81% (from 369 to 70 μm) when co-administered with Sunitinib.
Achieved 80% survival rate over 3 weeks (matching sunitinib alone) when co-administered with Sunitinib.
Did not alter vascular pruning or intratumoral hypoxia caused by anti-VEGF antibody or Sunitinib alone.
Prevented the increase in mesenchymal markers (Snail1, N-cadherin, vimentin) induced by VEGF inhibition.
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Animal Model:Nu/Nu nude mice (orthotopically injected with luciferase-expressing Panc-1 human pancreatic adenocarcinoma cells into the pancreas allowed to grow for 2-3 weeks until detectable before treatment)
[1] -
Dosage:30 mg/kg (single-agent; co-administered with Sunitinib); 40 mg/kg (Sunitinib)
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Administration:p.o.; daily; 3 weeks
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Result:Had little effect on tumor growth, vascularity, or intratumoral hypoxia when administered alone.
Reduced tumor growth more than Sunitinib alone (bioluminescence tumor burden was lower at all time points over 21 days) when co-administered with Sunitinib.
Reduced trapped acinar cell area density from ~4% to ~1% when co-administered with Sunitinib.
Eliminated micrometastases (detected in 4 of 6 mice treated with Sunitinib alone, but 0 of 6 mice treated with the combination) when co-administered with Sunitinib.
Maintained vascular pruning and intratumoral hypoxia similar toSunitinib alone when co-administered with Sunitinib.
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Animal Model:C57BL/6 mice (aged 4.8 months; induced by stereotactic intracranial injection of elastase (35 mU in 2.5 μL) into the basal cistern followed by subcutaneous implantation of an osmotic mini-pump delivering angiotensin II (1000 ng/kg/min))[3]
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Dosage:10 mg/kg
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Administration:p.o.; daily; 21 days or until euthanasia
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Result:Detected intracranial aneurysms in 94% of treated mice, with no significant difference from vehicle-treated mice.
Increased subarachnoid hemorrhage prevalence to 94%, which was significantly higher than the 64% in vehicle-treated mice.
Reduced survival rate to 25%, which was significantly lower than the 57% in vehicle-treated mice.
Showed no significant effect on systolic blood pressure or weight loss compared to vehicle-treated mice.
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Animal Model:Cells were trypsinized, resuspended in Coon’s F12with 5% FBS, 0.5% BBE and PSG, and injected into the right flank ofnude mice (5 × 106 cells per mouse); treatment initiated when tumors reached 200 to 400 mm3)
[4] -
Dosage:30 mg/kg (single dose); 45 mg/kg (daily)
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Administration:p.o.; single dose (30 mg/kg); daily (45 mg/kg)
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Result:Equally inhibited Met phosphorylation and downstream pAkt and pERK signaling in Met-amplified ATC allografts at single oral doses of 30 mg/kg or 45 mg/kg.
Caused significant tumor growth inhibition with daily oral 45 mg/kg dosing: vehicle-treated allografts showed ~25-fold tumor volume change, while treated allografts showed ~8-fold change.
Reduced tumor growth by ~68% relative to vehicle at day 15 with daily oral 45 mg/kg dosing.
Had no significant effect on Met-diploid ATC allografts.
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Animal Model:C57BL/6 (male, 8-10 weeks old, 23 g, gouty arthritis induced by intra-articular injection of MSU crystals)[5]
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Dosage:40 mg/kg
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Administration:p.o.; single dose; 12 h post-MSU challenge
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Result:Reduced neutrophil accumulation in the synovial cavity.
Increased the percentage of neutrophils with apoptotic morphology.
Increased efferocytosis rates of apoptotic neutrophils by macrophages.
Reduced periarticular tissue myeloperoxidase (MPO) activity, CXCL1 levels, and IL-1β levels.
Decreased histopathological joint inflammation scores.
Increased paw withdrawal mechanical thresholds.
Increased Annexin A1 expression in periarticular tissue, synovial macrophages (F4/80+) and neutrophils (Ly6G+).
Abrogated all induced effects (reduced neutrophils, increased apoptosis, reduced MPO and CXCL1 levels) when pretreated with caspase inhibitor zVAD-fmk.
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Animal Model:C57BL/6 (male, 8-10 weeks old, 23 g, neutrophilic pleurisy induced by intrapleural injection of LPS)[5]
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Dosage:40 mg/kg
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Administration:p.o.; single dose; 4 h post-LPS challenge; 90 h post-zymosan challenge
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Result:Reduced neutrophil accumulation in the pleural cavity.
Increased neutrophil apoptosis.
Increased efferocytosis of apoptotic neutrophils by macrophages.
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Animal Model:C57BL/6 (male, 8-10 weeks old, 23 g, peritonitis induced by intraperitoneal injection of zymosan)[5]
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Dosage:40 mg/kg
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Administration:p.o.; single dose; 90 h post-zymosan challenge
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Result:Increased efferocytosis rates, shown by a higher percentage of F4/80+CFSE+ macrophages.
Increased MFI of CFSE in macrophages.
Increased percentage of macrophages with ingested apoptotic thymocytes via morphological counting.
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Animal Model:Female nu/nu mice were injected subcutaneously in the right flank with GTL-16 human gastric carcinoma cells. When tumors reached approximately 250 mm3, mice were administered this compound by oral gavage in 0.5% methylcellulose suspension.
[6] -
Dosage:1, 3, 10 and 30 mg/kg (p.o., 16 days); 0.15, 1.5, 5 and15 mg/kg/d (s.c., 14 days); 0.3, 1, 3 and 10 mg/kg/d (p.o., 4 days)
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Administration:p.o.; once daily; 16 days; s.c.; continuous infusion; 14 days; p.o.; once daily; 4 days
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Result:Achieved 64%, 74%, 90%, and 100% tumor growth inhibition (TGI) at oral doses of 1 mg/kg/d, 3 mg/kg/d, 10 mg/kg/d, and 30 mg/kg/d, respectively.
Achieved 46%, 63%, 75%, and 93% TGI at continuous subcutaneous infusion doses of 0.5 mg/kg/d, 1.5 mg/kg/d, 5 mg/kg/d, and 15 mg/kg/d, respectively.
Inhibited c-Met phosphorylation with an EC50 of 10 nmol/L and EC90 of 45 nmol/L.
Reached EC50 of 13 nmol/L and EC90 of 80 nmol/L for TGI.
Correlated 90% inhibition of c-Met phosphorylation with 80% TGI.
Showed dose-dependent inhibition of downstream c-Met signaling molecules (phospho-Gab-1, phospho-AKT, phospho-Erk, phospho-PLCr1, phospho-STAT5).
Induced dose-dependent decrease in Ki67-positive proliferating cells.
Induced dose-dependent induction of cleaved caspase-3 (apoptosis marker).
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Animal Model:Athymic nude mice were implanted subcutaneously in the right flank with U87MG human glioblastoma cells; treatment was initiated when tumors reached approximately 170 mm3[6]
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Dosage:0.3, 1, 3, 10 and 30 mg/kg (p.o., 10 days); 5, 15 and 50 mg/kg (p.o., 3 days)
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Administration:p.o.; once daily; 10 days; p.o.; once daily; 3 days
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Result:Achieved 0%, 30%, 48%, 68%, and 84% TGI at oral doses of 0.3 mg/kg/d, 1 mg/kg/d, 3 mg/kg/d, 10 mg/kg/d, and 30 mg/kg/d, respectively.
Showed dose-dependent inhibition of c-Met, phospho-Gab-1, phospho-Erk1/2, and phospho-AKT.
Induced dose-dependent induction of cleaved caspase-3.
Observed strong dose-dependent increase in phospho-PDGFRβ levels, while phospho-EGFR levels remained unchanged.
Induced dose-dependent reductions in Ki67-positive proliferating cells and CD31-positive microvessel density (MVD), with significant reductions at 3, 10, and 30 mg/kg/d.
Showed dose-dependent reductions in plasma human IL-8 levels, with significant decreases at 3, 10, and 30 mg/kg/d.
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Animal Model:Athymic nude mice were implanted subcutaneously in the right flank with SW620 human colon carcinoma cells; treatment was initiated when tumors reached approximately 200 mm3[6]
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Dosage:40 mg/kg; 50 mg/kg
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Administration:p.o.; once daily; 25 days (40 mg/kg); 21 days (50 mg/kg)
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Result:Achieved 45% TGI.
Marked inhibition of c-Met phosphorylation maintained throughout the treatment period.
Increased total c-Met protein levels in tumors significantly following treatment, though no increase in MET gene copy number was observed.
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Animal Model:Athymic nude mice were implanted subcutaneously in the right flank with HT29 human colon carcinoma cells; treatment was initiated when tumors reached approximately 200 mm3.[6]
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Dosage:50 mg/kg
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Administration:p.o.; once daily; 21 days
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Result:Achieved 40% TGI as monotherapy, with significant inhibition of c-Met phosphorylation.
Increased phospho-AKT levels and did not induce tumor apoptosis as monotherapy.
Achieved 77% TGI when combined with RON shRNA knockdown, blocked phospho-AKT upregulation, and significantly increased cleaved caspase-3 levels.
RON shRNA alone achieved 52% TGI.
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Animal Model:Athymic nude mice were implanted subcutaneously in the right flank with Colo205 human colon carcinoma cells; treatment was initiated when tumors reached approximately 200 mm3.[6]
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Dosage:40 mg/kg
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Administration:p.o.; once daily; 18 days
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Result:Achieved 44% TGI.
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Animal Model:Athymic nude mice were implanted subcutaneously in the right flank with MDA-MB-231 human breast carcinoma cells; treatment was initiated when tumors reached approximately 200 mm3.[6]
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Dosage:40 mg/kg
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Administration:p.o.; once daily; 14 days
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Result:Achieved 43% TGI.
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Animal Model:Athymic nude mice were implanted subcutaneously in the right flank with H292 human non-small cell lung carcinoma cells; treatment was initiated when tumors reached approximately 200 mm3.[6]
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Dosage:50 mg/kg
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Administration:p.o.; once daily; 31 days
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Result:Achieved 39% TGI.
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Animal Model:Female nu/nu mice were injected subcutaneously in the right flank with GTL-16 human gastric carcinoma cells. When tumors reached approximately 250 mm3, mice were administered this compound by oral gavage in 0.5% methylcellulose suspension.[6]
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Dosage:1, 3, 10 and 30 mg/kg/d
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Administration:p.o.; multiple doses
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Result:Showed dose-dependent reductions in plasma human IL-8 and VEGFA levels.
Decreased plasma IL-8 levels significantly at 3 mg/kg/d and above.
Decreased plasma VEGFA levels significantly at 10 mg/kg/d and above.
Chemical Information
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CAS No. 1159490-83-1
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Molecular Weight 470.38
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Formula C19H19N8O5P
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SMILES
O=P(O)(O)O.OCCN1N=CC(C2=NC3=C(N=C2)N=NN3CC4=CC5=CC=CN=C5C=C4)=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (2)
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Journal Impact Factor
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Most Recent
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
JCI Insight
Injury-induced FoxM1 expression in mouse kidney drives epithelial proliferation by a Cyclin F dependent mechanism. [Abstract]2024 Jun 25;9(15):e175416. PMID: 38916959
Purity & Documentation
References
[1]. Sennino B, et al. Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer discovery. 2012 Mar;2(3):270-87. [Content Brief]
[2]. Sennino B, et al. Inhibition of c-Met reduces lymphatic metastasis in RIP-Tag2 transgenic mice. Cancer research. 2013 Jun 15;73(12):3692-703. [Content Brief]
[3]. Peña-Silva RA, et al. Novel role for endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms. Hypertension. 2015 Mar;65(3):587-93. [Content Brief]
[4]. Knauf JA, et al. Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers. The Journal of clinical investigation. 2018 Aug 31;128(9):4086-4097. [Content Brief]
[5]. Felix FB, et al. Blocking the HGF-MET pathway induces resolution of neutrophilic inflammation by promoting neutrophil apoptosis and efferocytosis. Pharmacological research. 2023 Feb;188:106640. [Content Brief]
[6]. Zou HY, et al. Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Molecular cancer therapeutics. 2012 Apr;11(4):1036-47. [Content Brief]
[7]. Wu Y, et al. Peptide-Functionalized Nanoinhibitor Restrains Brain Tumor Growth by Abrogating Mesenchymal-Epithelial Transition Factor (MET) Signaling. Nano letters. 2018 Sep 12;18(9):5488-5498. [Content Brief]
[8]. Lee NV, et al. A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells through [corrected] MAPK activation. PloS one. 2012;7(6):e39653. [Content Brief]
[9]. Timofeevski SL, et al. Enzymatic characterization of c-Met receptor tyrosine kinase oncogenic mutants and kinetic studies with aminopyridine and triazolopyrazine inhibitors. Biochemistry. 2009 Jun 16;48(23):5339-49. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PF-04217903 phosphate Related Classifications
HY-12017C Related Classifications
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