I-BET-726
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MedKoo CAT#: 525336

CAS#: 1300031-52-0

Description: I-BET-726, also known as GSK1324726A, is a potent and selective inhibitor of BET family proteins. Oral administration of I-BET726 to mouse xenograft models of human neuroblastoma results in tumor growth inhibition and down-regulation MYCN and BCL2 expression, suggesting a potential role for these genes in tumor growth.


Chemical Structure

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I-BET-726
CAS# 1300031-52-0

Theoretical Analysis

MedKoo Cat#: 525336
Name: I-BET-726
CAS#: 1300031-52-0
Chemical Formula: C25H23ClN2O3
Exact Mass: 434.14
Molecular Weight: 434.920
Elemental Analysis: C, 69.04; H, 5.33; Cl, 8.15; N, 6.44; O, 11.04

Price and Availability

Size Price Availability Quantity
5mg USD 250 2 Weeks
10mg USD 450 2 Weeks
50mg USD 1150 2 Weeks
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Synonym: I-BET-726; I-BET 726; I-BET726; GSK1324726A; GSK-1324726A; GSK 1324726A.

IUPAC/Chemical Name: 4-[(2S,4R)-1-Acetyl-4-[(4-chlorophenyl)amino]-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoic acid

InChi Key: FAWSUKOIROHXAP-NPMXOYFQSA-N

InChi Code: InChI=1S/C25H23ClN2O3/c1-15-13-23(27-21-10-8-20(26)9-11-21)22-14-19(7-12-24(22)28(15)16(2)29)17-3-5-18(6-4-17)25(30)31/h3-12,14-15,23,27H,13H2,1-2H3,(H,30,31)/t15-,23+/m0/s1

SMILES Code: O=C(O)C1=CC=C(C2=CC3=C(N(C(C)=O)[C@@H](C)C[C@H]3NC4=CC=C(Cl)C=C4)C=C2)C=C1

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

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:

Product Data:
Biological target: GSK1324726A is a novel, potent, and selective inhibitor of BET proteins with high affinity to BRD2 (IC50=41 nM), BRD3 (IC50=31 nM), and BRD4 (IC50=22 nM).
In vitro activity: In A431 cells, I-BET726 (50 nm) was significantly more potent in inhibiting cell viability (Fig. S1A) and proliferation (Fig. S1B) than even higher concentrations of JQ1 (500 nm), CPI203 (500 nm), and AZD5153 (100 nm). These results show that I-BET726 potently inhibits survival, proliferation and migration of established and primary human skin SCC cells. Reference: Cell Death Dis. 2020 May 5;11(5):318. https://pubmed.ncbi.nlm.nih.gov/32371868/
In vivo activity: In the CHP-212 model, treatment with 5 mg/kg I-BET726 resulted in TGI (tumor growth inhibition) equal to 50% (n=8; p= 0.1816; Figure 7C), and mice in the 15 mg/kg group exhibited a TGI of 82% at the end of the study (n=5; p =0.0488). Taken together, these data highlight the potential of BET inhibitors such as I-BET726 as potent anti-tumor agents in neuroblastoma, in part through the alteration of apoptotic and N-Myc-driven pathways. Reference: PLoS One. 2013 Aug 23;8(8):e72967. https://pubmed.ncbi.nlm.nih.gov/24009722/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 30.0 68.98
DMSO 52.3 120.33
DMSO:PBS (pH 7.2) (1:4) 0.2 0.46
Ethanol 15.0 34.49

Preparing Stock Solutions

The following data is based on the product molecular weight 434.92 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.

Recalculate based on batch purity %
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. Liu Z, Li P, Yang YQ, Cai S, Lin X, Chen MB, Guo H. I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo. Cell Death Dis. 2020 May 5;11(5):318. doi: 10.1038/s41419-020-2515-z. PMID: 32371868; PMCID: PMC7200671. 2. Gosmini R, Nguyen VL, Toum J, Simon C, Brusq JM, Krysa G, Mirguet O, Riou-Eymard AM, Boursier EV, Trottet L, Bamborough P, Clark H, Chung CW, Cutler L, Demont EH, Kaur R, Lewis AJ, Schilling MB, Soden PE, Taylor S, Walker AL, Walker MD, Prinjha RK, Nicodème E. The discovery of I-BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain inhibitor. J Med Chem. 2014 Oct 9;57(19):8111-31. doi: 10.1021/jm5010539. Epub 2014 Sep 24. PMID: 25249180. 3. Liu Z, Li P, Yang YQ, Cai S, Lin X, Chen MB, Guo H. I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo. Cell Death Dis. 2020 May 5;11(5):318. doi: 10.1038/s41419-020-2515-z. PMID: 32371868; PMCID: PMC7200671. 4. Wyce A, Ganji G, Smitheman KN, Chung CW, Korenchuk S, Bai Y, Barbash O, Le B, Craggs PD, McCabe MT, Kennedy-Wilson KM, Sanchez LV, Gosmini RL, Parr N, McHugh CF, Dhanak D, Prinjha RK, Auger KR, Tummino PJ. BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models. PLoS One. 2013 Aug 23;8(8):e72967. doi: 10.1371/journal.pone.0072967. PMID: 24009722; PMCID: PMC3751846.
In vitro protocol: 1. Liu Z, Li P, Yang YQ, Cai S, Lin X, Chen MB, Guo H. I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo. Cell Death Dis. 2020 May 5;11(5):318. doi: 10.1038/s41419-020-2515-z. PMID: 32371868; PMCID: PMC7200671. 2. Gosmini R, Nguyen VL, Toum J, Simon C, Brusq JM, Krysa G, Mirguet O, Riou-Eymard AM, Boursier EV, Trottet L, Bamborough P, Clark H, Chung CW, Cutler L, Demont EH, Kaur R, Lewis AJ, Schilling MB, Soden PE, Taylor S, Walker AL, Walker MD, Prinjha RK, Nicodème E. The discovery of I-BET726 (GSK1324726A), a potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain inhibitor. J Med Chem. 2014 Oct 9;57(19):8111-31. doi: 10.1021/jm5010539. Epub 2014 Sep 24. PMID: 25249180.
In vivo protocol: 1. Liu Z, Li P, Yang YQ, Cai S, Lin X, Chen MB, Guo H. I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo. Cell Death Dis. 2020 May 5;11(5):318. doi: 10.1038/s41419-020-2515-z. PMID: 32371868; PMCID: PMC7200671. 2. Wyce A, Ganji G, Smitheman KN, Chung CW, Korenchuk S, Bai Y, Barbash O, Le B, Craggs PD, McCabe MT, Kennedy-Wilson KM, Sanchez LV, Gosmini RL, Parr N, McHugh CF, Dhanak D, Prinjha RK, Auger KR, Tummino PJ. BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models. PLoS One. 2013 Aug 23;8(8):e72967. doi: 10.1371/journal.pone.0072967. PMID: 24009722; PMCID: PMC3751846.

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1: Chan KH, Zengerle M, Testa A, Ciulli A. Impact of target warhead and linkage
vector on inducing protein degradation: comparison of Bromodomain and
Extra-Terminal (BET) degraders derived from triazolodiazepine (JQ1) and
tetrahydroquinoline (I-BET726) BET inhibitor scaffolds. J Med Chem. 2017 Jun 8.
doi: 10.1021/acs.jmedchem.6b01912. [Epub ahead of print] PubMed PMID: 28595007.


2: Gosmini R, Nguyen VL, Toum J, Simon C, Brusq JM, Krysa G, Mirguet O,
Riou-Eymard AM, Boursier EV, Trottet L, Bamborough P, Clark H, Chung CW, Cutler
L, Demont EH, Kaur R, Lewis AJ, Schilling MB, Soden PE, Taylor S, Walker AL,
Walker MD, Prinjha RK, Nicodème E. The discovery of I-BET726 (GSK1324726A), a
potent tetrahydroquinoline ApoA1 up-regulator and selective BET bromodomain
inhibitor. J Med Chem. 2014 Oct 9;57(19):8111-31. doi: 10.1021/jm5010539. Epub
2014 Sep 24. PubMed PMID: 25249180.


3: Wyce A, Ganji G, Smitheman KN, Chung CW, Korenchuk S, Bai Y, Barbash O, Le B,
Craggs PD, McCabe MT, Kennedy-Wilson KM, Sanchez LV, Gosmini RL, Parr N, McHugh
CF, Dhanak D, Prinjha RK, Auger KR, Tummino PJ. BET inhibition silences
expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor
models. PLoS One. 2013 Aug 23;8(8):e72967. doi: 10.1371/journal.pone.0072967.
eCollection 2013. PubMed PMID: 24009722; PubMed Central PMCID: PMC3751846.