Synonym
GK921; GK-921; GK 921;
IUPAC/Chemical Name
3-(phenylethynyl)-2-(2-(pyrrolidin-1-yl)ethoxy)pyrido[2,3-b]pyrazine
InChi Key
MNYJJHBAEYKXEG-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H20N4O/c1-2-7-17(8-3-1)10-11-19-21(26-16-15-25-13-4-5-14-25)24-18-9-6-12-22-20(18)23-19/h1-3,6-9,12H,4-5,13-16H2
SMILES Code
C12=NC=CC=C1N=C(OCCN3CCCC3)C(C#CC4=CC=CC=C4)=N2
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
Biological target:
GK921 is a transglutaminase 2 (TGase) inhibitor with an IC50 of 7.71 μM for human recombinant TGase 2.
In vitro activity:
GK921 (Fig. 1a) showed TGase 2 inhibitory activity as 8.93 μM of IC50 under a modified assay condition, which concurred with a previous report (Supple Fig. 1a). Isothermal titration calorimetry (ITC) analysis also showed that GK921 binds TGase 2 in a dose-dependent manner (Fig. 1b). Cell proliferating assay using sulforhodamine B (SRB) showed that GK921 induced cell growth inhibition in RCC cells (Fig. 1c).
Reference: Amino Acids. 2018 Nov;50(11):1583-1594. https://pubmed.ncbi.nlm.nih.gov/30105541/
In vivo activity:
The results showed that GK921 inhibited the increase of Vimentin induced by bleomycin but upregulated the E-cadherin expression, which indicated that Gk921 could inhibit the EMT induced by bleomycin. The staining results suggested that GK921 could reduce pulmonary fibrosis induced by bleomycin in mice and reduce the production of collagen fibers (Fig. 7E–G).
Reference: Respir Physiol Neurobiol. 2020 May;276:103402. https://pubmed.ncbi.nlm.nih.gov/32006666/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
30.0 |
87.10 |
| DMSO |
31.5 |
91.46 |
| Ethanol |
30.0 |
87.10 |
| Ethanol:PBS (pH 7.2) (1:6) |
0.1 |
0.41 |
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
344.42
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. Kim N, Kang JH, Lee WK, Kim SG, Lee JS, Lee SH, Park JB, Kim KH, Gong YD, Hwang KY, Kim SY. Allosteric inhibition site of transglutaminase 2 is unveiled in the N terminus. Amino Acids. 2018 Nov;50(11):1583-1594. doi: 10.1007/s00726-018-2635-2. Epub 2018 Aug 14. PMID: 30105541.
2. Ku BM, Kim SJ, Kim N, Hong D, Choi YB, Lee SH, Gong YD, Kim SY. Transglutaminase 2 inhibitor abrogates renal cell carcinoma in xenograft models. J Cancer Res Clin Oncol. 2014 May;140(5):757-67. doi: 10.1007/s00432-014-1623-5. Epub 2014 Mar 8. PMID: 24610445.
3. Wang K, Zu C, Zhang Y, Wang X, Huan X, Wang L. Blocking TG2 attenuates bleomycin-induced pulmonary fibrosis in mice through inhibiting EMT. Respir Physiol Neurobiol. 2020 May;276:103402. doi: 10.1016/j.resp.2020.103402. Epub 2020 Jan 29. PMID: 32006666.
4. Kim SY. New Insights into Development of Transglutaminase 2 Inhibitors as Pharmaceutical Lead Compounds. Med Sci (Basel). 2018 Oct 8;6(4):87. doi: 10.3390/medsci6040087. PMID: 30297644; PMCID: PMC6313797.
In vitro protocol:
1. Kim N, Kang JH, Lee WK, Kim SG, Lee JS, Lee SH, Park JB, Kim KH, Gong YD, Hwang KY, Kim SY. Allosteric inhibition site of transglutaminase 2 is unveiled in the N terminus. Amino Acids. 2018 Nov;50(11):1583-1594. doi: 10.1007/s00726-018-2635-2. Epub 2018 Aug 14. PMID: 30105541.
2. Ku BM, Kim SJ, Kim N, Hong D, Choi YB, Lee SH, Gong YD, Kim SY. Transglutaminase 2 inhibitor abrogates renal cell carcinoma in xenograft models. J Cancer Res Clin Oncol. 2014 May;140(5):757-67. doi: 10.1007/s00432-014-1623-5. Epub 2014 Mar 8. PMID: 24610445.
In vivo protocol:
1. Wang K, Zu C, Zhang Y, Wang X, Huan X, Wang L. Blocking TG2 attenuates bleomycin-induced pulmonary fibrosis in mice through inhibiting EMT. Respir Physiol Neurobiol. 2020 May;276:103402. doi: 10.1016/j.resp.2020.103402. Epub 2020 Jan 29. PMID: 32006666.
2. Kim SY. New Insights into Development of Transglutaminase 2 Inhibitors as Pharmaceutical Lead Compounds. Med Sci (Basel). 2018 Oct 8;6(4):87. doi: 10.3390/medsci6040087. PMID: 30297644; PMCID: PMC6313797.
1: Ku BM, Kim SJ, Kim N, Hong D, Choi YB, Lee SH, Gong YD, Kim SY. Transglutaminase 2 inhibitor abrogates renal cell carcinoma in xenograft models. J Cancer Res Clin Oncol. 2014 May;140(5):757-67. doi: 10.1007/s00432-014-1623-5. PubMed PMID: 24610445.
2: Kang JH, Lee JS, Hong D, Lee SH, Kim N, Lee WK, Sung TW, Gong YD, Kim SY. Renal cell carcinoma escapes death by p53 depletion through transglutaminase 2-chaperoned autophagy. Cell Death Dis. 2016 Mar 31;7:e2163. doi: 10.1038/cddis.2016.14. PubMed PMID: 27031960; PubMed Central PMCID: PMC4823929.
3: Kang JH, Lee SH, Kim SY. Discovery of a novel target for renal cell carcinoma: transglutaminase 2. Cell Death Dis. 2016 Apr 21;7:e2200. doi: 10.1038/cddis.2016.99. PubMed PMID: 27100894; PubMed Central PMCID: PMC4855678.
