CC-930

CC-930, also known as Tanzisertib, is a potent, selective, and orally active JNK inhibitor with potential antifibrotic activity. CC-930 entered Phase I clinical trials. Tanzisertib may have potential use for prevention and treatment of dermal fibrosis. Selective inhibition of JNK by CC-930 exerted potent antifibrotic effects in vitro and in different models in vivo. JNK might thus be a novel molecular target for the treatment of fibrosis in SSc.

Product information

CAS Number: 899805-25-5

Molecular Weight: 448.44

Formula: C21H23F3N6O2

Synonym:

Tanzisertib

CC 930

JNK-930

JNKI1

JNKI 1

Chemical Name: (1S,4r)-4-((9-((S)-tetrahydrofuran-3-yl)-8-((2,4,6-trifluorophenyl)amino)-9H-purin-2-yl)amino)cyclohexanol JNK-930; JNKI-1

Smiles: OC1CCC(CC1)NC1=NC2=C(C=N1)N=C(NC1C(F)=CC(F)=CC=1F)N2[C@@H]1COCC1

InChiKey: IBGLGMOPHJQDJB-MOKVOYLWSA-N

InChi: InChI=1S/C21H23F3N6O2/c22-11-7-15(23)18(16(24)8-11)28-21-27-17-9-25-20(26-12-1-3-14(31)4-2-12)29-19(17)30(21)13-5-6-32-10-13/h7-9,12-14,31H,1-6,10H2,(H,27,28)(H,25,26,29)/t12?,13-,14?/m0/s1

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO: 89 mg/mLwarmed(183.54 mM). Water: 4 mg/mLwarmed(8.24 mM).

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:

CC-930 inhibits the formation of phospho-cJun in human PBMC stimulated by phorbol-12-myristate-13-acetate and phytohemeagglutinin (IC50=1 μM). CC-930 (1-2 μM) substantially reduces hepatocyte apoptosis and necrosis, abrogates apoptosis and necrosis in FC-loaded WT hepatocytes. CC-930 blocks the JNK pathway that is activated by pro-fibrotic cytokines in systemic sclerosis.

In Vivo:

CC-930 (10 and 30 mg/kg, p.o.) inhibits the production of TNFa by 23% and 77% in the acute rat LPS-induced TNFa production PK-PD model. CC-930 (150 mg/kg) prevents the development of fibrosis in different models, but can also induce the regression of pre-existing fibrosis.

References:

1. Gan LT, Van Rooyen DM, Koina M, McCuskey RS, Teoh NC, Farrell GC. Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent. J Hepatol. 2014 Jul 23. pii: S0168-8278(14)00523-6. doi: 10.1016/j.jhep.2014.07.024. [Epub ahead of print] PubMed PMID: 25064435.
2. Atsriku C, Hoffmann M, Ye Y, Kumar G, Surapaneni S. Metabolism and disposition of a potent and selective JNK inhibitor [14C]tanzisertib following oral administration to rats, dogs and humans. Xenobiotica. 2015 May;45(5):428-41. doi: 10.3109/00498254.2014.990949. PubMed PMID: 25482583.
3. Atsriku C, Hoffmann M, Moghaddam M, Kumar G, Surapaneni S. In vitro metabolism of a novel JNK inhibitor tanzisertib: interspecies differences in oxido-reduction and characterization of enzymes involved in metabolism. Xenobiotica. 2015;45(6):465-80. doi: 10.3109/00498254.2014.991367. PubMed PMID: 25475995.

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