Atuveciclib (BAY-1143572)

Atuveciclib (BAY-1143572) is potent and highly selective PTEFb/CDK9 inhibitor with IC50 values of 13 nM for CDK9/CycT and the ratio of IC50 values for CDK2/CDK9 is about 100. Outside the CDK family, It inhibits GSK3 kinase with IC50 values of 45 nM and 87 nM for GSK3α and GSK3β respectively.

Product information

CAS Number: 1414943-88-6

Molecular Weight: 387.43

Formula: C18H18FN5O2S

Chemical Name: [(3-{[4-(4-fluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl]amino}phenyl)methyl](imino)methyl-λ⁶-sulfanone

Smiles: COC1C=C(F)C=CC=1C1=NC(NC2C=C(CS(C)(=N)=O)C=CC=2)=NC=N1

InChiKey: ACWKGTGIJRCOOM-UHFFFAOYSA-N

InChi: InChI=1S/C18H18FN5O2S/c1-26-16-9-13(19)6-7-15(16)17-21-11-22-18(24-17)23-14-5-3-4-12(8-14)10-27(2,20)25/h3-9,11,20H,10H2,1-2H3,(H,21,22,23,24)

Technical Data

Appearance: Solid Power

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

Solubility: Solubility (25°C). 77 mg/mL(198.74 mM). Insoluble.

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:

BAY 1143572 is a potent and highly selective CDK9 inhibitor (IC50 CDK9/CycT1: 13 nM, ratio of IC50 values CDK2/CDK9: 100). Outside the CDK family, submicromolar inhibitory activity was only recorded against GSK3 kinase (IC50 GSK3α: 45 nM, GSK3β: 87 nM). BAY 1143572 demonstrates antiproliferative activity against HeLa cells (IC50 = 920 nM) and MOLM-13 cells (IC50 = 310 nM). It also demonstrates improved Caco-2 permeability and a decreased efflux ratio (PappA→B: 35 nm/s, ER: 6) relative to lead compound BAY‐958 (PappA→B: 22 nm/s, ER: 15).

In Vivo:

In an in vivo pharmacokinetic study in rats, BAY 1143572 showed low blood clearance (CLb 1.1 L/h/kg). The volumes of distribution (Vss) of BAY 1143572 is 1.0 L/kg. BAY 1143572 shows significantly improved oral bioavailability of 54 %. The blood/plasma ratios is about 1. It does not show significant inhibition of cytochrome P450 activity, with IC50 values >20 μM. The administration of BAY 1143572 in immunocompromized NOD/Shi-scid/IL-2Rγ null (NOG) mice xenografted with patient-derived ATL cells greatly reduced the infiltration of ATL cells into organs, such as liver and bone marrow. Decreased human soluble IL2R levels in serum were also observed, which indicated a reduction of ATL tumor burden.

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