CPI203

• CAS: 1446144-04-2
• Catalog Number: ACM1446144042
• Category: Inhibitors
• Molecular Weight: 399.90
• Molecular Formula: C19H18ClN5OS
• Description: CPI203, also known as TEN010, JQ-2; RO6870810 and RG6146, is a potent and orally active BET bromodomain inhibitor. CPI203 enhances the antiproliferative effects of rapamycin on human neuroendocrine tumors. CPI203 ownregulates Myc expression, causes G1 cell cycle arrest and attenuates cell proliferation in human pancreatic neuroendocrine tumors. CPI203 arrests the growth of T cell acute lymphoblastic leukemia cells in vitro (EC50 = 91.2 nM).
• Synonyms: CPI203; CPI-203; CPI 203; TEN010; TEN 010; TEN010; JQ-2; JQ 2; JQ2; RG-6146; RG 6146; RG-6146; RO6870810; RO-6870810; RO 6870810
• IUPAC Name: (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamide
• Canonical SMILES: O=C(N)C[C@H]1C2=NN=C(C)N2C3=C(C(C)=C(C)S3)C(C4=CC=C(Cl)C=C4)=N1
• InChI: InChI=1S/C19H18ClN5OS/c1-9-10(2)27-19-16(9)17(12-4-6-13(20)7-5-12)22-14(8-15(21)26)18-24-23-11(3)25(18)19/h4-7,14H,8H2,1-3H3,(H2,21,26)/t14-/m0/s1
• InChI Key: QECMENZMDBOLDR-AWEZNQCLSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: CPI-203 is a cell permeable inhibitor of BET bromodomain, with an IC50 value of ~37 nM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 57.07; H, 4.54; Cl, 8.86; N, 17.51; O, 4.00; S, 8.02
• Exact Mass: 399.09206
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To confirm the potential activation of CPI-203 on latent HIV-1 expression, this study investigated the effects of CPI-203 on well-established latently infected Jurkat T cell lines, including J-Lat A2 and 10.6 cells. J-Lat A2 cells contain a single provirus integrated into the intron of RNPS1 and an EGFP gene under the control of the HIV-1 long terminal repeat (LTR). The percentages of GFP-positive cells in these two cell lines after treatment with CPI-203 at different concentrations were analyzed by flow cytometry. The magnitude of reactivation induced by 10 ng/ml of PMA was defined as 100% reactivation, and an obvious dose-dependent increase in the percentage of GFP-positive cells treated with CPI-203 was observed compared to the background levels (Fig. 1A, C). As shown in Fig. 1A, when the CPI-203 concentration increased from 0.01 μM to 25 μM, the percentage of GFP-positive cells increased from 32.47% to 61.98%. Notably, CPI-203 was shown to induce HIV-1 reactivation more potently than JQ1, which is known as a BETi to reactivate HIV-1 from latency. Correspondingly, when the JQ1 concentration increased from 0.01 μM to 5 μM, the percentage of GFP-positive cells increased from 30.86% to 50.37%.; Reference: Biochem Pharmacol. 2019 Jun;164:237-251. https://pubmed.ncbi.nlm.nih.gov/30991051/
• In Vivo Activity: This study first confirmed the activity of this compound in HSCs by culturing sorted LSK CD150+ CD48- cells from Erg+/- and Erg+/+ mice in the presence of 0.5 μM CPI-203 for 24 h. As expected, Myc mRNA was reduced by twofold to threefold compared with mock-treated HSCs in both groups, while there was no difference in Myc expression between the Erg+/- and Erg+/+ groups (Fig. 6A). The study next treated Ergfl/fl and Ergfl/fl; Mx1Cre mice with CPI-203 simultaneously with Erg deletion through pIpC injection (Fig. 6B). Strikingly, CPI-203 restored the numbers of immunophenotypic HSCs (defined as c-Kit+ EPCR+ CD150+ CD48-, since Sca-1 expression is not reliable shortly after pIpC administration) to normal levels in ErgΔ/Δ BM while increasing HSC numbers in Ergfl/fl controls (Fig. 6C). Similarly, CPI-203 rescued the numbers of immunophenotypic Erg+/- HSCs (LSK CD150+ CD48-) to normal levels and again increased HSC numbers in control animals (Fig. 6D,E). These experiments clearly demonstrate that a reduction of MYC activity can indeed rescue the effect of Erg deletion on HSC numbers, likely through an anti-differentiation mode of action.; Reference: Genes Dev. 2015 Sep 15;29(18):1915-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579349/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).