PVTX-405
Based on 1 Customer Validation
PVTX-405 is a selective and oral active IKZF2 molecular glue degrader with a DC50 of 0.7 nM and a Dmax of 91%. PVTX-405 enhances degradation efficiency, significantly reduces off-target degradation, and alleviates hERG inhibition with IC50 of 48 µM. PVTX-405 significantly inhibits the growth of MC38 tumors, with greater synergistic anti-cancer efficacy in combination with immune checkpoint therapies (ICTs) (anti-PD1 or anti-LAG3) in the MC38 mouse tumor xenograft model using Crbn391V C57BL/6 mice.
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- Purity: 97.07%
- CAS No.: 2991021-08-8
- 화학식: C30H31N5O4
- 분자량:525.60
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보관:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
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IZKF2 0.7 nM (DC50) |
kv11.1 48 μM (IC50) |
PVTX-405 (Compound 16a) (0.017 nM-10 μM, 6 h) has superior neo-substrate selectivity, with minimal effect in reducing levels of IKZF1, IKZF3, GSPT1 and CK1α proteins (Dmax of <20% at up to 10 µM)[1].
PVTX-405 (0.01-10000 nM, 1-6 h) CRBN-dependently degrades IKZF2 (DC50: 6.3 nM and Dmax: 65%) with maximal degradation by 3 h in Jurkat cells[1].
PVTX-405 (1-1000 nM, 24 h) effectively regulates an established IKZF2 transcriptional target, increases inflammatory cytokine IL-2 and reduces the suppressive activity of Tregs, leading to an increase in Teff cell proliferation in Jurkat T cells[1].
PVTX-405 (0.1-1000 nM, 3-6 h) dose-dependently degrades IKZF2, destabilizes human Tregs cells, and induces the proliferation of Teff cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | Vd | Clearance (CL) | AUC | Plasma Concentration | Bioavailability | T1/2 |
|---|---|---|---|---|---|---|---|---|
| Cynomolgus Monkey | 1 mg/kg | i.v. | 8.1 L/kg | 19 mL/min/kg | / | / | / | / |
| Cynomolgus Monkey | 3 mg/kg | p.o. | / | / | 1289 ng·h/mL | 111 ng/mL | 50 % | 10 h |
| Mice | 1 mg/kg | i.v. | 2.7 L/kg | 19 mL/min/kg | / | / | / | / |
| Mice | 3 mg/kg | p.o. | / | / | 1997 ng·h/mL | 600 ng/mL | 76 % | 3.8 h |
| Rat | 1 mg/kg | i.v. | 2.9 mL/min/kg | 20 mL/min/kg | / | / | / | / |
| Rat | 3 mg/kg | p.o. | / | / | 2765 ng·h/mL | 417 ng/mL | 118 % | 2.6 h |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Crbn391V C57BL/6 mice were implanted subcutaneously with MC38 cells (5 × 106/mouse)[1].
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Dosage:30 mg/kg
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Administration:Oral gavage (p.o.), once a day for 21 days and then measured tumor sizes and animal weights1.
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Result:Significantly suppressed MC38 tumor growth, with 68% of tumor growth inhibition at the end of treatment.
Did not induce any weight loss and other signs of toxicity during the duration of dosing in CrbnI391V mice.
Significantly delayed the time required for tumors to reach 2000 mm3, improved survival of animals and showed more complete responses in combination with either Anti-PD1 or Anti-LAG3 as compared to both two antibody alone.
Chemical Information
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CAS No. 2991021-08-8
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Appearance Solid
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분자량 525.60
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화학식 C30H31N5O4
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Color White to off-white
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SMILES
O=C1C2=CC=C(C(OC3)=C2CN1[C@@H]4C(NC(CC4)=O)=O)C3(CC5)CCN5CC6=CC(C7=CN(N=C7)C)=CC=C6
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
순도&문서
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Data Sheet (272 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PVTX-405 Related Classifications
HY-172930 Related Classifications
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