GK921
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MedKoo CAT#: 530358

CAS#: 1025015-40-0

Description: GK921 is a transglutaminase 2 (TGase 2) inhibitor. GK921 showed cytotoxicity to RCC (average GI50 in eight RCC cell lines: 0.905 μM). A single treatment with GK921 almost completely reduced tumor growth by stabilizing p53 in the ACHN and CAKI-1 preclinical xenograft tumor models. TGase 2 inhibitor GK921 abrogates RCC growth in xenograft tumor models, suggesting the possibility of a new therapeutic approach to RCC.


Chemical Structure

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GK921
CAS# 1025015-40-0

Theoretical Analysis

MedKoo Cat#: 530358
Name: GK921
CAS#: 1025015-40-0
Chemical Formula: C21H20N4O
Exact Mass: 344.16
Molecular Weight: 344.418
Elemental Analysis: C, 73.23; H, 5.85; N, 16.27; O, 4.65

Price and Availability

Size Price Availability Quantity
100mg USD 950
200mg USD 1650
500mg USD 2450
1g USD 3250
2g USD 4850
5g USD 6450
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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

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: 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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. 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

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.

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. 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.

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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.