NMS-P528
NMS-P528 is a DNA minor groove alkylating agent and ADC payload. NMS-P528 undergoes intramolecular cyclization to form reactive electrophilic derivatives, which in turn induce DNA damage, cell cycle arrest, and Apoptosis. NMS-P528 shows no significant anti-tumor activity as a free payload in a HER2-negative Raji lymphoma mouse xenograft model. NMS-P528 serves as the cytotoxic payload for the antibody-drug conjugate EV20/NMS-P945. NMS-P528 can be used in research related to breast cancer, gastric cancer, colon adenocarcinoma, Burkitt's lymphoma, neuroblastoma, pancreatic cancer, prostate cancer, head and neck cancer, ovarian cancer, and melanoma.
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- CAS No.: 1466546-45-1
- Formule: C27H28ClN3O3S
- Masse moléculaire:510.05
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
NMS-P528 (gradient concentrations; 72 h) potently inhibits the proliferation of a panel of 30 distinct tumor cell lines, with a mean IC50 of 0.202 nM following 72-hour treatment[1].
NMS-P528 (gradient concentrations; 72-144 h) circumvents multi-drug resistance in A2780/ADR ovarian cancer cells, and exhibits similar antiproliferative activity against parental A2780 cells, with resistance indices of 1.2 (72 h) and 1.8 (144 h)[1].
NMS-P528 (30 μM; up to 24 h) has a short plasma half-life in mouse, rat, and cynomolgus monkey plasma, which are 0.46, 0.22, and 0.34 h respectively, due to rapid spirocyclization and subsequent inactivation[1].
NMS-P528 (gradient concentrations; 144 h) potently inhibits the proliferation of the tumor cell lines HCC1569, HCC1954, NCI-N87, Hs-578-T and SW620, with a mean IC50 value ranging from 0.010 to 0.025 nM after 144 h of treatment[1].
NMS-P528 (1 nM; 24-72 h) induces DNA damage, cell cycle arrest and apoptosis in HCC1954 breast cancer cells, which is evidenced by increased positive rate of p-H2AX, decreased BrdUrd incorporation and expanded sub-G1 cell population[1].
NMS-P528 induces apoptosis in human neuroblastoma cell lines SK-N-AS, COG-N-453, NBL-S, Felix and NB-1 at its IC50 concentration, which is confirmed by an increased annexin V-positive rate[2].
NMS-P528, delivered via EV20/NMS-P945, exerts potent, target-dependent cytotoxic activity against a variety of tumor cell lines in vitro, with stronger activity in HER-3-highly expressing cells including MDA-MB-435, Sk-mel 24, DU145, Fadu, OVCAR-8, SNU638 and WM115[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:30 diverse human tumor cell lines
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Concentration:Scalar concentrations
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Incubation Time:72 h
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Result:Showed high antiproliferative activity across all tested cell lines, with an average IC50 value of 0.202 nmol/L.
Outperformed reference agents DXd (average IC50: 148 nmol/L) and doxorubicin (average IC50: 200 nmol/L).
Exhibited potency comparable to MMAE (average IC50: 0.393 nmol/L).
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Cell Line:Multidrug-resistant A2780/ADR ovarian cancer cells, parental A2780 ovarian cancer cells
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Concentration:Scalar concentrations
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Incubation Time:72 h; 144 h
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Result:Demonstrated similar antiproliferative activity in chemoresistant A2780/ADR cells and parental A2780 cells, with a resistance index (RI) of 1.2 at 72 hours and 1.8 at 144 hours.
Showed no significant multidrug resistance dependency, in contrast to MMAE, DXd, and doxorubicin which had RIs of 241/258, 12/20, and 83/99 at 72/144 hours, respectively.
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Cell Line:Human tumor cell lines (HCC1569, HCC1954, NCI-N87, Hs-578-T, SW620)
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Concentration:Scalar concentrations
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Incubation Time:144 h
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Result:Exhibited potent antiproliferative activity across all tested cell lines, with average IC50 values of 0.025 nmol/L (HCC1569), 0.012 nmol/L (HCC1954), 0.024 nmol/L (NCI-N87), 0.024 nmol/L (Hs-578-T), and 0.010 nmol/L (SW620).
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Cell Line:HCC1954 breast cancer cells
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Concentration:1 nmol/L
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Incubation Time:24 to 72 h
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Result:Reduced BrdUrd incorporation (a marker of active S-phase) from 21% in untreated cells to 7% in treated cells, inducing cell-cycle block.
Increased p-H2AX-positive cells from 3% in untreated cells to 39% in treated cells, indicating DNA damage.
Elevated sub-G1 phase cells from 7% to 21%, inducing apoptosis.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID mice (4-week-old female; subcutaneous inoculation with 5×106 Raji cells)[1]
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Dosage:0.5 mg/kg
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Administration:i.v.; single dose
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Result:Exhibited no tumor growth inhibition (TGI).
Chemical Information
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CAS No. 1466546-45-1
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Masse moléculaire 510.05
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Formule C27H28ClN3O3S
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SMILES
ClC[C@@H](C1=C2C=C(O)C3=C1C(C)=CS3)CN2C(C(N4)=CC5=C4C=CC(OCCN6CCCC6)=C5)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Valsasina B, et al. Novel Thienoduocarmycin-Trastuzumab ADC Demonstrates Strong Antitumor Efficacy with Favorable Safety Profile in Preclinical Studies. Molecular cancer therapeutics. 2023 Dec 01;22(12):1465-1478. [Content Brief]
[2]. Sano R, et al. An antibody-drug conjugate directed to the ALK receptor demonstrates efficacy in preclinical models of neuroblastoma. Science translational medicine. 2019 Mar 13;11(483):eaau9732. [Content Brief]
[3]. Capone E, et al. EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors. Pharmaceutics. 2021 Apr 02;13(4):483. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
NMS-P528 Related Classifications
HY-156249 Related Classifications
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- NMS-P528
- 1466546-45-1
- ADC Payloads
- DNA/RNA Synthesis
- DNA Alkylator/Crosslinker
- Apoptosis
- apoptosis
- multidrug resistance systems
- breast carcinoma
- tumor cell lines
- Burkitt lymphoma
- human neuroblastoma cell lines
- Raji lymphoma mouse xenograft model
- cell-cycle block
- DNA damage
- DNA minor groove adenine
- Inhibitor
- inhibitor
- inhibit