CDK4/6-IN-15

• CAT Number: I042323
• CAS Number: 2078047-99-9
• Molecular Formula: C21H27FN8S
• Molecular Weight: 442.56
• Purity: ≥95%
• Synonyms: 5-[2-[[5-[4-(dimethylamino)piperidin-1-yl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-N,4-dimethyl-1,3-thiazol-2-amine
• InChI: InChI=1S/C21H27FN8S/c1-13-19(31-21(23-2)26-13)18-16(22)12-25-20(28-18)27-17-6-5-15(11-24-17)30-9-7-14(8-10-30)29(3)4/h5-6,11-12,14H,7-10H2,1-4H3,(H,23,26)(H,24,25,27,28)
• InChIKey: NAGFLZVMWVHHLW-UHFFFAOYSA-N
• SMILES: CC1=C(SC(=N1)NC)C2=NC(=NC=C2F)NC3=NC=C(C=C3)N4CCC(CC4)N(C)C

CDK4/6-IN-15 is an orally active and selective CDK4/6 inhibitor. CDK4/6-IN-15 potently inhibits cancer cells growth. CDK4/6-IN-15 arrests cell cycle at G1 phase and suppresses retinoblastoma tumour suppressor protein (Rb) phosphorylation at S780 and E2 factor (E2F)-regulated gene expression[1].
CDK4/6-IN-15 (compound 91) (10 μM; 24 h) also potently inhibits FLT3 and MYLK4 with inhibition rates >90%[1].
CDK4/6-IN-15 (0-5 μM; 72 h) suppresses tumour cell proliferation selectively with GI50s of 0.107 μM (MV4-11) and 0.325 μM (MDA-MB-453)[1].
CDK4/6-IN-15 (0.1-1 μM; 24 h) arrests exclusively the cell cycle at G1 phase in Rb-positive MV4-11 cells and MDA-MB-453 cells[1].
CDK4/6-IN-15 (0.1-1 μM or 0.3-3 μM; 24-96 h) triggers apoptosis in MV4-11 and MDA-MB-453 cells[1].
CDK4/6-IN-15 (0.1-3.3 μM; 4-24 h) inhibits phosphorylation of Rb[1].
CDK4/6-IN-15 (compound 91) (2 mg/kg for i.v. or 10 mg/kg for p.o.; single dose) shows comparable oral absorption in healthy male adult BALB/c mice (20-25 g) as well as (5 mg/kg for i.v. or 200 mg/kg for p.o.; single dose) in male albino Wistar rats (250-350 g)[1].

Pharmacokinetic Analysis[1]

Route
Dose (mg/kg)
CL (mL/min/kg)
Vss (L/kg)
AUC (μM·h)
Cmax (μM)
Tmax (h)
t1/2 (h)
F (%)

rat
IV
5
155
27.5
1.2
1.4
/
2.1
/

PO
20
/
/
4.4
0.3
4.3
20.3
95

mouse
IV
2
90
15.7
0.7
1.3
/
2.9
/

PO
10
/
/
4.3
0.6
2.5
2.7
129

Reference

[1]. Tadesse S, et al. Discovery and pharmacological characterization of a novel series of highly selective inhibitors of cyclin-dependent kinases 4 and 6 as anticancer agents. Br J Pharmacol. 2018 Jun;175(12):2399-2413.
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