S63845 is a potent and selective myeloid cell leukemia 1 (MCL1) inhibitor with a Kd of 0.19 nM for human MCL1.

Product information

CAS Number: 1799633-27-4

Molecular Weight: 829.26

Formula: C39H37ClF4N6O6S

Chemical Name: (2R)-2-[(5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl}-6-(5-fluorofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl)oxy]-3-(2-{[1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl]methoxy}phenyl)propanoic acid

Smiles: CN1CCN(CCOC2=CC=C(C3=C(SC4=NC=NC(O[C@H](CC5=CC=CC=C5OCC5=CC=NN5CC(F)(F)F)C(O)=O)=C34)C3=CC=C(F)O3)C(C)=C2Cl)CC1

InChiKey: ZFBHXVOCZBPADE-SSEXGKCCSA-N

InChi: InChI=1S/C39H37ClF4N6O6S/c1-23-26(7-8-28(34(23)40)53-18-17-49-15-13-48(2)14-16-49)32-33-36(45-22-46-37(33)57-35(32)29-9-10-31(41)55-29)56-30(38(51)52)19-24-5-3-4-6-27(24)54-20-25-11-12-47-50(25)21-39(42,43)44/h3-12,22,30H,13-21H2,1-2H3,(H,51,52)/t30-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 33.33 mg/mL (40.19 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

The pro-survival protein myeloid cell leukemia 1 (MCL1) is over expressed in many cancers. S63845 is a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. The activity of S63845 is next evaluated in a panel of eight AML cell lines: all lines are sensitive to S63845 (IC50=4-233 nM).

In Vivo:

S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Intravenously injected (i.v.) S63845 exerts dose-dependent anti-tumour activity in human multiple myeloma (H929 and AMO1) xenografts in immunocompromised mice, with maximal tumour growth inhibition of 114% in the AMO1 model and 103% in the H929 model. At 25 mg/kg, S63845 induces complete regression in 7 out of 8 of the mice at 100 days after treatment in the AMO1 model.

Products are for research use only. Not for human use.