TEN010 | CPI203 | RG6146 | JQ-2 | CAS#1446144-04-2 | BET bromodomain inhibitor

MedKoo Cat#: 407122 | Name: CPI203

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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).

Chemical Structure

CPI203

CAS#1446144-04-2

Theoretical Analysis

MedKoo Cat#: 407122

Name: CPI203

CAS#: 1446144-04-2

Chemical Formula: C19H18ClN5OS

Exact Mass: 399.0921

Molecular Weight: 399.90

Elemental Analysis: C, 57.07; H, 4.54; Cl, 8.86; N, 17.51; O, 4.00; S, 8.02

Price and Availability

Size	Price	Availability
5mg	USD 120.00	Ready to ship
10mg	USD 190.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship
500mg	USD 3,450.00	Ready to ship

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Synonym

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/Chemical 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

InChi Key

QECMENZMDBOLDR-AWEZNQCLSA-N

InChi Code

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

SMILES Code

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

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

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.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

TEN-010 binds to the acetylated lysine recognition motifs found in the bromodomain of BET proteins, which prevents the interaction between BET proteins and acetylated histones. This interaction disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB70223

QC Data

View QC data: current batch, Lot#CRB70223

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

CPI-203 is a cell permeable inhibitor of BET bromodomain, with an IC50 value of ~37 nM.

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	47.8	119.40
	DMF	30.0	75.02
	DMF:PBS (pH 7.2) (1:1)	0.5	1.25
	Ethanol	35.0	87.52

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 399.90 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Hua P, Hester J, Adigbli G, Li R, Psaila B, Roy A, Bataille CJR, Wynne GM, Jackson T, Milne TA, Russell AJ, Davies J, Roberts I, Issa F, Watt SM. The BET inhibitor CPI203 promotes ex vivo expansion of cord blood long-term repopulating HSCs and megakaryocytes. Blood. 2020 Nov 19;136(21):2410-2415. doi: 10.1182/blood.2020005357. PMID: 32599615. 2. Liang T, Zhang X, Lai F, Lin J, Zhou C, Xu X, Tan X, Liu S, Li L. A novel bromodomain inhibitor, CPI-203, serves as an HIV-1 latency-reversing agent by activating positive transcription elongation factor b. Biochem Pharmacol. 2019 Jun;164:237-251. doi: 10.1016/j.bcp.2019.04.005. Epub 2019 Apr 13. PMID: 30991051. 3. Nakagawa A, Adams CE, Huang Y, Hamarneh SR, Liu W, Von Alt KN, Mino-Kenudson M, Hodin RA, Lillemoe KD, Fernández-Del Castillo C, Warshaw AL, Liss AS. Selective and reversible suppression of intestinal stem cell differentiation by pharmacological inhibition of BET bromodomains. Sci Rep. 2016 Feb 9;6:20390. doi: 10.1038/srep20390. PMID: 26856877; PMCID: PMC4746593. 4. Knudsen KJ, Rehn M, Hasemann MS, Rapin N, Bagger FO, Ohlsson E, Willer A, Frank AK, Søndergaard E, Jendholm J, Thorén L, Lee J, Rak J, Theilgaard-Mönch K, Porse BT. ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation. Genes Dev. 2015 Sep 15;29(18):1915-29. doi: 10.1101/gad.268409.115. PMID: 26385962; PMCID: PMC4579349.

In vitro protocol:

In vivo protocol:

1. Nakagawa A, Adams CE, Huang Y, Hamarneh SR, Liu W, Von Alt KN, Mino-Kenudson M, Hodin RA, Lillemoe KD, Fernández-Del Castillo C, Warshaw AL, Liss AS. Selective and reversible suppression of intestinal stem cell differentiation by pharmacological inhibition of BET bromodomains. Sci Rep. 2016 Feb 9;6:20390. doi: 10.1038/srep20390. PMID: 26856877; PMCID: PMC4746593. 2. Knudsen KJ, Rehn M, Hasemann MS, Rapin N, Bagger FO, Ohlsson E, Willer A, Frank AK, Søndergaard E, Jendholm J, Thorén L, Lee J, Rak J, Theilgaard-Mönch K, Porse BT. ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation. Genes Dev. 2015 Sep 15;29(18):1915-29. doi: 10.1101/gad.268409.115. PMID: 26385962; PMCID: PMC4579349.

1: Wong C, Laddha SV, Tang L, Vosburgh E, Levine AJ, Normant E, Sandy P, Harris CR, Chan CS, Xu EY. The bromodomain and extra-terminal inhibitor CPI203 enhances the antiproliferative effects of rapamycin on human neuroendocrine tumors. Cell Death Dis. 2014 Oct 9;5:e1450. doi: 10.1038/cddis.2014.396. PubMed PMID: 25299775; PubMed Central PMCID: PMC4237236. 2: Moros A, Rodríguez V, Saborit-Villarroya I, Montraveta A, Balsas P, Sandy P, Martínez A, Wiestner A, Normant E, Campo E, Pérez-Galán P, Colomer D, Roué G. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Oct;28(10):2049-59. doi: 10.1038/leu.2014.106. Epub 2014 Mar 18. PubMed PMID: 24721791.