WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406102
CAS#: 910232-84-7
Description: CGI1746 is a small-molecule Btk inhibitor chemotype with a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 has exquisite selectivity for Btk and inhibits both auto- and transphosphorylation steps necessary for enzyme activation.
MedKoo Cat#: 406102
Name: CGI1746
CAS#: 910232-84-7
Chemical Formula: C34H37N5O4
Exact Mass: 579.28455
Molecular Weight: 579.69
Elemental Analysis: C, 70.45; H, 6.43; N, 12.08; O, 11.04
Synonym: CGI1746; CGI-1746; CGI 1746.
IUPAC/Chemical Name: 4-(tert-butyl)-N-(2-methyl-3-(4-methyl-6-((4-(morpholine-4-carbonyl)phenyl)amino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)benzamide
InChi Key: JIFCFQDXHMUPGP-UHFFFAOYSA-N
InChi Code: InChI=1S/C34H37N5O4/c1-22-27(7-6-8-28(22)37-31(40)23-9-13-25(14-10-23)34(2,3)4)29-21-38(5)33(42)30(36-29)35-26-15-11-24(12-16-26)32(41)39-17-19-43-20-18-39/h6-16,21H,17-20H2,1-5H3,(H,35,36)(H,37,40)
SMILES Code: O=C(NC1=CC=CC(C(N=C2NC3=CC=C(C(N4CCOCC4)=O)C=C3)=CN(C)C2=O)=C1C)C5=CC=C(C(C)(C)C)C=C5
Appearance: White to off-white 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
| Biological target: | CGI-1746 is an inhibitor of the Btk with IC50 of 1.9 nM. |
| In vitro activity: | Next, this study asked whether CGI1746 inhibits HMCLs in vitro. Treatment of ARP1 and OPM2 cells with a dose range of drug (0.2 μM to 50 μM; 48 hrs) resulted in similar levels of cytotoxicity in both cell lines (IC50 ≅ 10 μM; Figure 1B). Reference: Cancer Res. 2015 Feb 1; 75(3): 594–604. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384656/ |
| In vivo activity: | To testify CGI-1746 in vivo, this study xenografted OCI-MY5 cells subcutaneously into NSG mice respectively (n = 5), CGI-1476 treatment was start 7 days after injection. Tumor diameter was measured twice per week to evaluate the tumor growth rate. After 30 days, the tumors from control group, PBS Treatment, were visibly smaller than their counterparts (Figure 6C). The average weight of control tumors and the ratio of tumor weight to body weight were higher than the treatment tumors (Figure 6D & 6E). Time course analysis of tumor growth demonstrated that CGI-1746 outstandingly lagged the MM tumor growth in vivo (Figure 6F). Reference: Oncotarget. 2017 Aug 22; 8(34): 56858–56867. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593608/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 58.33 | 100.62 | |
| DMSO:PBS (pH 7.2) (1:3) | 0.25 | 0.43 | |
| DMF | 25.0 | 43.13 | |
| Ethanol | 16.63 | 28.69 |
The following data is based on the product molecular weight 579.69 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. Yang Y, Shi J, Gu Z, Salama ME, Das S, Wendlandt E, Xu H, Huang J, Tao Y, Hao M, Franqui R, Levasseur D, Janz S, Tricot G, Zhan F. Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple myeloma. Cancer Res. 2015 Feb 1;75(3):594-604. doi: 10.1158/0008-5472.CAN-14-2362. Epub 2015 Jan 14. PMID: 25589346; PMCID: PMC4384656. 2. Di Paolo JA, Huang T, Balazs M, Barbosa J, Barck KH, Bravo BJ, Carano RA, Darrow J, Davies DR, DeForge LE, Diehl L, Ferrando R, Gallion SL, Giannetti AM, Gribling P, Hurez V, Hymowitz SG, Jones R, Kropf JE, Lee WP, Maciejewski PM, Mitchell SA, Rong H, Staker BL, Whitney JA, Yeh S, Young WB, Yu C, Zhang J, Reif K, Currie KS. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol. 2011 Jan;7(1):41-50. doi: 10.1038/nchembio.481. Epub 2010 Nov 28. PMID: 21113169. 3. Gu C, Peng H, Lu Y, Yang H, Tian Z, Yin G, Zhang W, Lu S, Zhang Y, Yang Y. BTK suppresses myeloma cellular senescence through activating AKT/P27/Rb signaling. Oncotarget. 2017 May 23;8(34):56858-56867. doi: 10.18632/oncotarget.18096. PMID: 28915637; PMCID: PMC5593608. |
| In vitro protocol: | 1. Yang Y, Shi J, Gu Z, Salama ME, Das S, Wendlandt E, Xu H, Huang J, Tao Y, Hao M, Franqui R, Levasseur D, Janz S, Tricot G, Zhan F. Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple myeloma. Cancer Res. 2015 Feb 1;75(3):594-604. doi: 10.1158/0008-5472.CAN-14-2362. Epub 2015 Jan 14. PMID: 25589346; PMCID: PMC4384656. 2. Di Paolo JA, Huang T, Balazs M, Barbosa J, Barck KH, Bravo BJ, Carano RA, Darrow J, Davies DR, DeForge LE, Diehl L, Ferrando R, Gallion SL, Giannetti AM, Gribling P, Hurez V, Hymowitz SG, Jones R, Kropf JE, Lee WP, Maciejewski PM, Mitchell SA, Rong H, Staker BL, Whitney JA, Yeh S, Young WB, Yu C, Zhang J, Reif K, Currie KS. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol. 2011 Jan;7(1):41-50. doi: 10.1038/nchembio.481. Epub 2010 Nov 28. PMID: 21113169. |
| In vivo protocol: | 1. Gu C, Peng H, Lu Y, Yang H, Tian Z, Yin G, Zhang W, Lu S, Zhang Y, Yang Y. BTK suppresses myeloma cellular senescence through activating AKT/P27/Rb signaling. Oncotarget. 2017 May 23;8(34):56858-56867. doi: 10.18632/oncotarget.18096. PMID: 28915637; PMCID: PMC5593608. 2. Yang Y, Shi J, Gu Z, Salama ME, Das S, Wendlandt E, Xu H, Huang J, Tao Y, Hao M, Franqui R, Levasseur D, Janz S, Tricot G, Zhan F. Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple myeloma. Cancer Res. 2015 Feb 1;75(3):594-604. doi: 10.1158/0008-5472.CAN-14-2362. Epub 2015 Jan 14. PMID: 25589346; PMCID: PMC4384656. |
1: Di Paolo JA, Huang T, Balazs M, Barbosa J, Barck KH, Bravo BJ, Carano RA, Darrow J, Davies DR, DeForge LE, Diehl L, Ferrando R, Gallion SL, Giannetti AM, Gribling P, Hurez V, Hymowitz SG, Jones R, Kropf JE, Lee WP, Maciejewski PM, Mitchell SA, Rong H, Staker BL, Whitney JA, Yeh S, Young WB, Yu C, Zhang J, Reif K, Currie KS. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol. 2011 Jan;7(1):41-50. doi: 10.1038/nchembio.481. Epub 2010 Nov 28. PubMed PMID: 21113169.
