Mcl-1 inhibitor 6

• CAT Number: I045381
• CAS Number: 2598978-56-2
• Molecular Formula: C26H28ClNO6S
• Molecular Weight: 518.02
• Purity: ≥95%
• Synonyms: 4-(4-acetylphenyl)sulfonyl-1-[3-(4-chloro-3,5-dimethylphenoxy)propyl]-3,5-dimethylpyrrole-2-carboxylic acid
• InChI: InChI=1S/C26H28ClNO6S/c1-15-13-21(14-16(2)23(15)27)34-12-6-11-28-18(4)25(17(3)24(28)26(30)31)35(32,33)22-9-7-20(8-10-22)19(5)29/h7-10,13-14H,6,11-12H2,1-5H3,(H,30,31)
• InChIKey: MKUKBCVJQXCFKM-UHFFFAOYSA-N
• SMILES: CC1=CC(=CC(=C1Cl)C)OCCCN2C(=C(C(=C2C(=O)O)C)S(=O)(=O)C3=CC=C(C=C3)C(=O)C)C

Mcl-1 inhibitor 6 is an orally active, selective myeloid cell leukemia 1 (Mcl-1) protein inhibitor with a Kd of 0.23 nM and a Ki of 0.02 μM. Mcl-1 inhibitor 6 possesses superior selectivity over other Bcl-2 family members (Bcl-2, Bcl2A1, Bcl-xL, and Bcl-w, Kd>10 μM). Mcl-1 inhibitor 6 is a potent antitumor agent[1].
Mcl-1 inhibitor 6 has Kis of 10 μM and 1.57μM for Bcl-2 and Bfl-1, respectively[1].
Mcl-1 inhibitor 6 (1, 5 μM; for 48 h) significantly induces apoptosis in a concentration-dependent manner[1].
Mcl-1 inhibitor 6 (0.1, 5 μM; for 4 h) remarkably upregulates PARP cleavage in H929 cells in a concentration-dependent manner[1].
Mcl-1 inhibitor 6 (for 72 h) shows antiproliferative activities against the tumor cell lines (H929, MV4-11, SK-BR-3, NCI-H23; IC50=0.36-3.02 μM). Mcl-1 inhibitor 6 shows ideal selectivity against CML cell line K562 (IC50>30 μM)[1].
Mcl-1 inhibitor 6 (compound 40; 60 mg/kg with PO or 20 mg/kg with IP; every two days for 14 days) shows desired in vivo tumor growth inhibition activity[1].
Mcl-1 inhibitor 6 (3 mg/kg with IV or 10 mg/kg with PO) has a T1/2 of 2.3 hours, a CL of 15.18 mL/min•kg by IV[1].

Reference

[1]. Peng-Ju Zhu, et al. Discovery of 3,5-Dimethyl-4-Sulfonyl-1 H-Pyrrole-Based Myeloid Cell Leukemia 1 Inhibitors with High Affinity, Selectivity, and Oral Bioavailability. J Med Chem. 2021 Aug 12;64(15):11330-11353.
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