WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206036
CAS#: 1088965-37-0
Description: GSK-923295, also known as GSK-923295A, is a novel antimitotic inhibitor of centromere-associated protein E (CENP-E) with potential anticancer activity. GSK923295A demonstrated significant antitumor activity against solid tumor models, inducing CRs in Ewing sarcoma, rhabdoid, and rhabdomyosarcoma xenografts. Clinical study showed that GSK923295 had dose-proportional pharmacokinetics and a low number of grade 3 or 4 adverse events. The observed incidence of myelosuppression and neuropathy was low. Further investigations may provide a more complete understanding of the potential for GSK923295 as an antiproliferative agent.
Hodoodo Cat#: H206036
Name: GSK-923295
CAS#: 1088965-37-0
Chemical Formula: C32H38ClN5O4
Exact Mass: 591.26
Molecular Weight: 592.130
Elemental Analysis: C, 64.91; H, 6.47; Cl, 5.99; N, 11.83; O, 10.81
Synonym: GSK923295; GSK 923295; GSK-923295; GSK-923295A; GSK923295A; GSK 923295A.
IUPAC/Chemical Name: 3-Chloro-N-{(1S)-2-[(N,N-dimethylglycyl)amino]-1-[(4-{8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl}-4-[(1-methylethyl)oxy]benzamide
InChi Key: WHMXDBPHBVLYRC-OFVILXPXSA-N
InChi Code: InChI=1S/C32H38ClN5O4/c1-20(2)42-29-13-12-24(16-27(29)33)32(41)35-25(17-34-30(40)19-37(4)5)15-22-8-10-23(11-9-22)28-18-38-14-6-7-26(21(3)39)31(38)36-28/h6-14,16,18,20-21,25,39H,15,17,19H2,1-5H3,(H,34,40)(H,35,41)/t21-,25-/m0/s1
SMILES Code: O=C(N[C@@H](CC1=CC=C(C2=CN3C=CC=C([C@@H](O)C)C3=N2)C=C1)CNC(CN(C)C)=O)C4=CC=C(OC(C)C)C(Cl)=C4
Appearance: Solid powder
Purity: >97% (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: >5 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:
| Biological target: | GSK-923295 is a special, allosteric inhibitor of centromere-associated protein-E (CENP-E) kinesin motor ATPase activity, with Ki of 3.2±0.2 nM and 1.6± 0.1 nM for human and canine, respectively. |
| In vitro activity: | To assess the response of liver tumor to CENP-E inhibitor, the growth inhibitory activity of GSK923295 was evaluated in 3 HCC cell lines after 24, 48, and 96 hours of continuous exposure [Figure 1A]. The IC50 of HepG2, LM3, and HUH7 were 7.5, 5.9, and 2.9 μM, respectively. After comparing with the HCC cell proliferation rates, no correlation was observed (P = 0.161), suggesting that there might be unidentified and dominant factors in determining growth inhibitory effect of GSK923295. After exposure to GSK923295 for 8 hours, a large fraction of the HCC cells had proceeded into G2/M-phase. Accordingly, a significantly upregulation of the mitotic marker cyclin B1 and pHH3 was observed [Figure 1B]. Reference: Chin Med J (Engl). 2019 Feb 5;132(3):311-318. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30681497/ |
| In vivo activity: | To further assess antitumor activity of GSK923295 in vivo, the inhibitor was administered to mice bearing xenografts of the LM3 tumor cells. Compared the vehicle group, mice with tumor showed significantly delayed tumor volume after GSK923295 treatment [Figure 1C], with clearly increasing in the abundance of mitotic figures morphologically in tumors [Figure 1E]. The subcutaneous tumor size was calculated and recorded every 2 days, and the results demonstrated that 125 mg/kg GSK923295 caused delay on HCC tumor-growth instead of regressions [Figure 1D], because no regressions occurred in six mice treated when the study was limited on 19th day. Reference: Chin Med J (Engl). 2019 Feb 5;132(3):311-318. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30681497/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 30.0 | 50.66 | |
| Ethanol | 11.8 | 20.00 |
The following data is based on the product molecular weight 592.13 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: | |
| In vitro protocol: | 1. Tang JC, Wu K, Zheng X, Xu M, Dai Y, Wei SS, Cai XJ. GSK923295 as a potential antihepatocellular carcinoma agent causing delay on liver regeneration after partial hepatectomy. Chin Med J (Engl). 2019 Feb 5;132(3):311-318. doi: 10.1097/CM9.0000000000000053. PMID: 30681497; PMCID: PMC6595801. 2. Wood KW, Lad L, Luo L, Qian X, Knight SD, Nevins N, Brejc K, Sutton D, Gilmartin AG, Chua PR, Desai R, Schauer SP, McNulty DE, Annan RS, Belmont LD, Garcia C, Lee Y, Diamond MA, Faucette LF, Giardiniere M, Zhang S, Sun CM, Vidal JD, Lichtsteiner S, Cornwell WD, Greshock JD, Wooster RF, Finer JT, Copeland RA, Huang PS, Morgans DJ Jr, Dhanak D, Bergnes G, Sakowicz R, Jackson JR. Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44. doi: 10.1073/pnas.0915068107. Epub 2010 Feb 18. PMID: 20167803; PMCID: PMC2851928. |
| In vivo protocol: | 1. Tang JC, Wu K, Zheng X, Xu M, Dai Y, Wei SS, Cai XJ. GSK923295 as a potential antihepatocellular carcinoma agent causing delay on liver regeneration after partial hepatectomy. Chin Med J (Engl). 2019 Feb 5;132(3):311-318. doi: 10.1097/CM9.0000000000000053. PMID: 30681497; PMCID: PMC6595801. 2. Wood KW, Lad L, Luo L, Qian X, Knight SD, Nevins N, Brejc K, Sutton D, Gilmartin AG, Chua PR, Desai R, Schauer SP, McNulty DE, Annan RS, Belmont LD, Garcia C, Lee Y, Diamond MA, Faucette LF, Giardiniere M, Zhang S, Sun CM, Vidal JD, Lichtsteiner S, Cornwell WD, Greshock JD, Wooster RF, Finer JT, Copeland RA, Huang PS, Morgans DJ Jr, Dhanak D, Bergnes G, Sakowicz R, Jackson JR. Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44. doi: 10.1073/pnas.0915068107. Epub 2010 Feb 18. PMID: 20167803; PMCID: PMC2851928. |
1: Mayes PA, Degenhardt YY, Wood A, Toporovskya Y, Diskin SJ, Haglund E, Moy C, Wooster R, Maris JM. Mitogen-activated protein kinase (MEK/ERK) inhibition sensitizes cancer cells to centromere-associated protein E inhibition. Int J Cancer. 2013 Feb 1;132(3):E149-57. doi: 10.1002/ijc.27781. Epub 2012 Sep 28. PubMed PMID: 22948716.
2: Chung V, Heath EI, Schelman WR, Johnson BM, Kirby LC, Lynch KM, Botbyl JD, Lampkin TA, Holen KD. First-time-in-human study of GSK923295, a novel antimitotic inhibitor of centromere-associated protein E (CENP-E), in patients with refractory cancer. Cancer Chemother Pharmacol. 2012 Mar;69(3):733-41. doi: 10.1007/s00280-011-1756-z. Epub 2011 Oct 22. PubMed PMID: 22020315.
3: Lock RB, Carol H, Morton CL, Keir ST, Reynolds CP, Kang MH, Maris JM, Wozniak AW, Gorlick R, Kolb EA, Houghton PJ, Smith MA. Initial testing of the CENP-E inhibitor GSK923295A by the pediatric preclinical testing program. Pediatr Blood Cancer. 2012 Jun;58(6):916-23. doi: 10.1002/pbc.23176. Epub 2011 May 16. PubMed PMID: 21584937; PubMed Central PMCID: PMC3163687.
4: Balamuth NJ, Wood A, Wang Q, Jagannathan J, Mayes P, Zhang Z, Chen Z, Rappaport E, Courtright J, Pawel B, Weber B, Wooster R, Sekyere EO, Marshall GM, Maris JM. Serial transcriptome analysis and cross-species integration identifies centromere-associated protein E as a novel neuroblastoma target. Cancer Res. 2010 Apr 1;70(7):2749-58. doi: 10.1158/0008-5472.CAN-09-3844. Epub 2010 Mar 16. PubMed PMID: 20233875; PubMed Central PMCID: PMC2848992.
5: Wood KW, Lad L, Luo L, Qian X, Knight SD, Nevins N, Brejc K, Sutton D, Gilmartin AG, Chua PR, Desai R, Schauer SP, McNulty DE, Annan RS, Belmont LD, Garcia C, Lee Y, Diamond MA, Faucette LF, Giardiniere M, Zhang S, Sun CM, Vidal JD, Lichtsteiner S, Cornwell WD, Greshock JD, Wooster RF, Finer JT, Copeland RA, Huang PS, Morgans DJ Jr, Dhanak D, Bergnes G, Sakowicz R, Jackson JR. Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5839-44. doi: 10.1073/pnas.0915068107. Epub 2010 Feb 18. PubMed PMID: 20167803; PubMed Central PMCID: PMC2851928.
