MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 205520 | Name: Galunisertib
Featured New

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Galunisertib, also known as LY2157299, is a novel, selective small molecule transforming growth factor beta receptor (TGF-βR) kinase inhibitor. LY2157299 inhibited HCC cell migration on Laminin-5, Fibronectin, Vitronectin, Fibrinogen and Collagen-I and de novo phosphorylation of pSMAD2. LY2157299 inhibited HCC migration and cell growth independently of the expression levels of TGF-βRII.

Chemical Structure

Galunisertib
Galunisertib
CAS#700874-72-2 (free base)

Theoretical Analysis

MedKoo Cat#: 205520

Name: Galunisertib

CAS#: 700874-72-2 (free base)

Chemical Formula: C22H19N5O

Exact Mass: 369.1590

Molecular Weight: 369.42

Elemental Analysis: C, 71.53; H, 5.18; N, 18.96; O, 4.33

Price and Availability

Size Price Availability Quantity
50mg USD 150.00 Ready to ship
100mg USD 250.00 Ready to ship
200mg USD 450.00 Ready to ship
500mg USD 950.00 Ready to ship
1g USD 1,650.00 Ready to ship
2g USD 2,950.00 Ready to Ship
5g USD 5,650.00 Ready to Ship
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
700874-72-2 (free base) 924898-09-9 (hydrate)
Synonym
LY2157299; LY-2157299; LY 2157299; Galunisertib
IUPAC/Chemical Name
4-(2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline-6-carboxamide
InChi Key
IVRXNBXKWIJUQB-UHFFFAOYSA-N
InChi Code
InChI=1S/C22H19N5O/c1-13-4-2-5-18(25-13)21-20(19-6-3-11-27(19)26-21)15-9-10-24-17-8-7-14(22(23)28)12-16(15)17/h2,4-5,7-10,12H,3,6,11H2,1H3,(H2,23,28)
SMILES Code
O=C(C1=CC=C2N=CC=C(C3=C(CCC4)N4N=C3C5=NC(C)=CC=C5)C2=C1)N
Appearance
Grey to brown 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
More Info
LY2157299 is a novel selective small molecule transforming growth factor beta receptor (TGF-βR) kinase inhibitor. LY-2157299 could inhibit TGF-β-mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells. Furthermore, in vivo administration of LY-2157299 ameliorated anemia in a TGF-β overexpressing transgenic mouse model of bone marrow failure. Most importantly, treatment with LY-2157199 stimulated hematopoiesis from primary MDS bone marrow specimens. These studies demonstrate that reduction in SMAD7 is a novel molecular alteration in MDS that leads to ineffective hematopoiesis by activating of TGF-β signaling in hematopoietic cells. These studies also illustrate the therapeutic potential of TBRI inhibitors in MDS. (source: Cancer Res. 2011 Feb 1;71(3):955-63. Epub 2010 Dec 28. ).    
Biological target:
TGF-β receptor type I (TGF-βRI) kinase inhibitor with an IC50 of 56 nM.
In vitro activity:
The combination of a small molecule inhibitor of TGF-β receptor I, Galunisertib, and CAR T cells was used to explore whether Galunisertib could enhance CAR T cell function against solid tumor cells. In vitro experiments showed Galunisertib could significantly enhance the specific cytotoxicity of both CD133- and HER2-specific CAR T cells. However, Galunisertib had no direct killing effect on target cells. Galunisertib significantly increased the cytokine secretion of CAR T cells and T cells that do not express CAR (Nontransfected T cells). Galunisertib did not affect the proliferation of T cells, the antigen expression on target cells and CD69 on CAR T cells. It was found that TGF-β was secreted by T cells themselves upon activation, and Galunisertib could reduce TGF-β signaling in CAR T cells. Reference: Eur J Histochem. 2020 Jun 19; 64(Suppl 2): 3122. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388644/
In vivo activity:
The in vivo antitumor efficacy of galunisertib was evaluated using a dose of 75 mg/kg administered twice daily by oral gavage, the dosing schedule defined by the PK/PD profile described in the pSMAD inhibition assays (Figure (Figure4).4). Monotherapy anti-tumor activity of galunisertib was evaluated in three independent models; the immune competent 4T1 syngenic murine breast cancer model, the MX1 human xenograft breast cancer model, and the Calu6 human xenograft lung cancer model. In each of these established tumor models, galunisertib monotherapy resulted in significant tumor growth delay (Figure 7A, 7B, 7C, and and7D).7D). For MX1, galunisertib monotherapy resulted in tumor growth delay of 10.3±4.3 days (1500 mm3 crossing time, p = 0.014) (Figure (Figure7A)7A) and for Calu6 galunisertib monotherapy resulted in tumor growth delay of 8.3 +/− 2.6 days (500 mm3 crossing time, p = 0.034) (Figure (Figure7B);7B); for 4T1, galunisertib monotherapy resulted in a tumor growth delay of 13±2.4 days (500 mm3 crossing time, p < 0.01 by repeated measures analysis) and a survival advantage of 4.5 days (p = 0.01) (Figure 7C, 7D), demonstrating the antitumor activity of the compound in traditional preclinical tumor models. Reference: Oncotarget. 2018 Jan 23; 9(6): 6659–6677. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805504/
Solvent mg/mL mM
Solubility
DMSO 24.0 65.00
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 369.42 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. Wang Z, Liu Q, Risu N, Fu J, Zou Y, Tang J, Li L, Liu H, Zhou G, Zhu X. Galunisertib enhances chimeric antigen receptor-modified T cell function. Eur J Histochem. 2020 Jun 19;64(s2):3122. doi: 10.4081/ejh.2020.3122. PMID: 32705856; PMCID: PMC7388644.
In vitro protocol:
1. Wang Z, Liu Q, Risu N, Fu J, Zou Y, Tang J, Li L, Liu H, Zhou G, Zhu X. Galunisertib enhances chimeric antigen receptor-modified T cell function. Eur J Histochem. 2020 Jun 19;64(s2):3122. doi: 10.4081/ejh.2020.3122. PMID: 32705856; PMCID: PMC7388644.
In vivo protocol:
1. Yingling JM, McMillen WT, Yan L, Huang H, Sawyer JS, Graff J, Clawson DK, Britt KS, Anderson BD, Beight DW, Desaiah D, Lahn MM, Benhadji KA, Lallena MJ, Holmgaard RB, Xu X, Zhang F, Manro JR, Iversen PW, Iyer CV, Brekken RA, Kalos MD, Driscoll KE. Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class transforming growth factor-β receptor type I inhibitor. Oncotarget. 2017 Dec 31;9(6):6659-6677. doi: 10.18632/oncotarget.23795. PMID: 29467918; PMCID: PMC5805504.
1: Harding JJ, Do RK, Yaqubie A, Cleverly A, Zhao Y, Gueorguieva I, Lahn M, Benhadji KA, Kelley RK, Abou-Alfa GK. Phase 1b study of galunisertib and ramucirumab in patients with advanced hepatocellular carcinoma. Cancer Med. 2021 Apr 2. doi: 10.1002/cam4.3880. Epub ahead of print. PMID: 33811482. 2: Melisi D, Oh DY, Hollebecque A, Calvo E, Varghese A, Borazanci E, Macarulla T, Merz V, Zecchetto C, Zhao Y, Gueorguieva I, Man M, Gandhi L, Estrem ST, Benhadji KA, Lanasa MC, Avsar E, Guba SC, Garcia-Carbonero R. Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti- PD-L1 antibody durvalumab in metastatic pancreatic cancer. J Immunother Cancer. 2021 Mar;9(3):e002068. doi: 10.1136/jitc-2020-002068. PMID: 33688022; PMCID: PMC7944986. 3: Reiss KA, Wattenberg MM, Damjanov N, Prechtel Dunphy E, Jacobs-Small M, Lubas MJ, Robinson J, Dicicco L, Garcia-Marcano L, Giannone MA, Karasic TB, Furth EE, Carpenter EL, Wojcieszynski AP, Vonderheide RH, Beatty GL, Ben-Josef E. A Pilot Study of Galunisertib plus Stereotactic Body Radiotherapy in Patients with Advanced Hepatocellular Carcinoma. Mol Cancer Ther. 2021 Feb;20(2):389-397. doi: 10.1158/1535-7163.MCT-20-0632. Epub 2020 Dec 2. PMID: 33268571; PMCID: PMC7867621. 4: Hira SK, Rej A, Paladhi A, Singh R, Saha J, Mondal I, Bhattacharyya S, Manna PP. Galunisertib Drives Treg Fragility and Promotes Dendritic Cell-Mediated Immunity against Experimental Lymphoma. iScience. 2020 Sep 29;23(10):101623. doi: 10.1016/j.isci.2020.101623. PMID: 33089111; PMCID: PMC7559877. 5: Wang Z, Liu Q, Risu N, Fu J, Zou Y, Tang J, Li L, Liu H, Zhou G, Zhu X. Galunisertib enhances chimeric antigen receptor-modified T cell function. Eur J Histochem. 2020 Jun 19;64(s2):3122. doi: 10.4081/ejh.2020.3122. PMID: 32705856; PMCID: PMC7388644. 6: PLOS ONE Staff. Correction: Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-βRI inhibitor galunisertib. PLoS One. 2020 Jun 25;15(6):e0235580. doi: 10.1371/journal.pone.0235580. Erratum for: PLoS One. 2020 Mar 25;15(3):e0222259. PMID: 32584902; PMCID: PMC7316286. 7: Masuda A, Nakamura T, Abe M, Iwamoto H, Sakaue T, Tanaka T, Suzuki H, Koga H, Torimura T. Promotion of liver regeneration and anti‑fibrotic effects of the TGF‑β receptor kinase inhibitor galunisertib in CCl4‑treated mice. Int J Mol Med. 2020 Jul;46(1):427-438. doi: 10.3892/ijmm.2020.4594. Epub 2020 May 5. PMID: 32377696. 8: Giannelli G, Santoro A, Kelley RK, Gane E, Paradis V, Cleverly A, Smith C, Estrem ST, Man M, Wang S, Lahn MM, Raymond E, Benhadji KA, Faivre S. Biomarkers and overall survival in patients with advanced hepatocellular carcinoma treated with TGF-βRI inhibitor galunisertib. PLoS One. 2020 Mar 25;15(3):e0222259. doi: 10.1371/journal.pone.0222259. Erratum in: PLoS One. 2020 Jun 25;15(6):e0235580. PMID: 32210440; PMCID: PMC7094874. 9: Wick A, Desjardins A, Suarez C, Forsyth P, Gueorguieva I, Burkholder T, Cleverly AL, Estrem ST, Wang S, Lahn MM, Guba SC, Capper D, Rodon J. Phase 1b/2a study of galunisertib, a small molecule inhibitor of transforming growth factor- beta receptor I, in combination with standard temozolomide-based radiochemotherapy in patients with newly diagnosed malignant glioma. Invest New Drugs. 2020 Oct;38(5):1570-1579. doi: 10.1007/s10637-020-00910-9. Epub 2020 Mar 5. PMID: 32140889; PMCID: PMC7497674. 10: Gueorguieva I, Tabernero J, Melisi D, Macarulla T, Merz V, Waterhouse TH, Miles C, Lahn MM, Cleverly A, Benhadji KA. Population pharmacokinetics and exposure-overall survival analysis of the transforming growth factor-β inhibitor galunisertib in patients with pancreatic cancer. Cancer Chemother Pharmacol. 2019 Nov;84(5):1003-1015. doi: 10.1007/s00280-019-03931-1. Epub 2019 Sep 3. PMID: 31482224. 11: Santini V, Valcárcel D, Platzbecker U, Komrokji RS, Cleverly AL, Lahn MM, Janssen J, Zhao Y, Chiang A, Giagounidis A, Guba SC, Gueorguieva I, Girvan AC, da Silva Ferreira M, Bhagat TD, Pradhan K, Steidl U, Sridharan A, Will B, Verma A. Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes. Clin Cancer Res. 2019 Dec 1;25(23):6976-6985. doi: 10.1158/1078-0432.CCR-19-1338. Epub 2019 Sep 3. PMID: 31481511. 12: Bhardwaj RM, McMahon JA, Nyman J, Price LS, Konar S, Oswald IDH, Pulham CR, Price SL, Reutzel-Edens SM. A Prolific Solvate Former, Galunisertib, under the Pressure of Crystal Structure Prediction, Produces Ten Diverse Polymorphs. J Am Chem Soc. 2019 Sep 4;141(35):13887-13897. doi: 10.1021/jacs.9b06634. Epub 2019 Aug 21. PMID: 31394896. 13: Li W, Tibben M, Wang Y, Lebre MC, Rosing H, Beijnen JH, Schinkel AH. P-glycoprotein (MDR1/ABCB1) controls brain accumulation and intestinal disposition of the novel TGF-β signaling pathway inhibitor galunisertib. Int J Cancer. 2020 Mar 15;146(6):1631-1642. doi: 10.1002/ijc.32568. Epub 2019 Jul 15. PMID: 31304590. 14: Kelley RK, Gane E, Assenat E, Siebler J, Galle PR, Merle P, Hourmand IO, Cleverly A, Zhao Y, Gueorguieva I, Lahn M, Faivre S, Benhadji KA, Giannelli G. A Phase 2 Study of Galunisertib (TGF-β1 Receptor Type I Inhibitor) and Sorafenib in Patients With Advanced Hepatocellular Carcinoma. Clin Transl Gastroenterol. 2019 Jul;10(7):e00056. doi: 10.14309/ctg.0000000000000056. PMID: 31295152; PMCID: PMC6708671. 15: Park JH, Kim MS, Ham S, Park ES, Kim KL, Suh W. Transforming Growth Factor β Receptor Type I Inhibitor, Galunisertib, Has No Beneficial Effects on Aneurysmal Pathological Changes in Marfan Mice. Biomol Ther (Seoul). 2019 Jul 9;28(1):98-103. doi: 10.4062/biomolther.2019.042. Epub ahead of print. PMID: 31284709; PMCID: PMC6939689. 16: Tibben MM, Huijberts S, Li W, Schinkel AH, Gebretensae A, Rosing H, Beijnen JH. Liquid chromatography-tandem mass spectrometric assay for the quantification of galunisertib in human plasma and the application in a pre-clinical study. J Pharm Biomed Anal. 2019 Sep 5;173:169-175. doi: 10.1016/j.jpba.2019.05.037. Epub 2019 May 21. PMID: 31146172. 17: Faivre S, Santoro A, Kelley RK, Gane E, Costentin CE, Gueorguieva I, Smith C, Cleverly A, Lahn MM, Raymond E, Benhadji KA, Giannelli G. Novel transforming growth factor beta receptor I kinase inhibitor galunisertib (LY2157299) in advanced hepatocellular carcinoma. Liver Int. 2019 Aug;39(8):1468-1477. doi: 10.1111/liv.14113. Epub 2019 Jun 3. PMID: 30963691. 18: Melisi D, Garcia-Carbonero R, Macarulla T, Pezet D, Deplanque G, Fuchs M, Trojan J, Kozloff M, Simionato F, Cleverly A, Smith C, Wang S, Man M, Driscoll KE, Estrem ST, Lahn MMF, Benhadji KA, Tabernero J. TGFβ receptor inhibitor galunisertib is linked to inflammation- and remodeling-related proteins in patients with pancreatic cancer. Cancer Chemother Pharmacol. 2019 May;83(5):975-991. doi: 10.1007/s00280-019-03807-4. Epub 2019 Mar 18. PMID: 30887178. 19: Melisi D, Garcia-Carbonero R, Macarulla T, Pezet D, Deplanque G, Fuchs M, Trojan J, Oettle H, Kozloff M, Cleverly A, Smith C, Estrem ST, Gueorguieva I, Lahn MMF, Blunt A, Benhadji KA, Tabernero J. Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer. Br J Cancer. 2018 Nov;119(10):1208-1214. doi: 10.1038/s41416-018-0246-z. Epub 2018 Oct 15. PMID: 30318515; PMCID: PMC6251034. 20: Ikeda M, Morimoto M, Tajimi M, Inoue K, Benhadji KA, Lahn MMF, Sakai D. A phase 1b study of transforming growth factor-beta receptor I inhibitor galunisertib in combination with sorafenib in Japanese patients with unresectable hepatocellular carcinoma. Invest New Drugs. 2019 Feb;37(1):118-126. doi: 10.1007/s10637-018-0636-3. Epub 2018 Jul 11. PMID: 29995286; PMCID: PMC6510840.