CCF-642

CCF-642 is a protein disulfide isomerase (PDI) inhibitor. CCF642 exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. In vitro, CCF642 inhibited PDI reductase activity about 100-fold more potently than the structurally distinct established inhibitors PACMA 31 and LOC14. CCF642 displayed potent efficacy in an aggressive syngeneic mouse model of multiple myeloma and prolonged the lifespan of C57BL/KaLwRij mice engrafted with 5TGM1-luc myeloma, an effect comparable to the first-line multiple myeloma therapeutic bortezomib.

Product information

CAS Number: 346640-08-2

Molecular Weight: 378.45

Formula: C15H10N2O4S3

Synonym:

CCF642

CCF-642

CCF 642

Chemical Name: 3-(4-Methoxyphenyl)-5-[(5-nitro-2-thienyl)methylene]-2-thioxo-4-thiazolidinone

Smiles: COC1C=CC(=CC=1)N1C(=S)SC(=CC2=CC=C(S2)[N+]([O-])=O)C1=O

InChiKey: SPYIETQLOVDJCF-WQLSENKSSA-N

InChi: InChI=1S/C15H10N2O4S3/c1-21-10-4-2-9(3-5-10)16-14(18)12(24-15(16)22)8-11-6-7-13(23-11)17(19)20/h2-8H,1H3/b12-8-

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO

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: ≥360 days 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:

CCF642 (3 μM; 0.5-6 hours) increases PERK dimerization by phosphorylation and IRE1-α oligomerization within 30 minutes in KMS-12-PE confirming accumulation of misfolded ER proteins. CCF642, a bone marrow-sparing compound, exhibits a submicromolar IC50 in 10 of 10 multiple myeloma cell lines (MM1.S, MM1.R, KMS-12-PE, KMS-12-BM, NCI-H929, U266, RPMI 8226, JJN-3, HRMM.09-luc, 5TGM1-luc).

In Vivo:

CCF642 (10 mg/kg; i.p.; three times a week; for 24 days) significantly prolongs life of 5TGM1-luc-bearing mice and suppresses 5TGM1-luc growth as determined by life imaging.

References:

1. Vatolin S, Phillips JG, Jha BK, Govindgari S, Hu J, Grabowski D, Parker Y, Lindner DJ, Zhong F, Distelhorst CW, Smith MR, Cotta C, Xu Y, Chilakala S, Kuang RR, Tall S, Reu FJ. Novel Protein Disulfide Isomerase Inhibitor with Anticancer Activity in Multiple Myeloma. Cancer Res. 2016 Jun1 ; 76(11):3340-50. doi: 10.1158/0008-5472.CAN-15-3099. Epub 2016 Apr 6. PubMed PMID: 27197150.

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