Entospletinib
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MedKoo CAT#: 206107

CAS#: 1229208-44-9

Description: Entospletinib, also known as GS-9973, is a highly selective and orally efficacious Syk inhibitor which is currently undergoing clinical evaluation for autoimmune and oncology indications. In Phase II clinical trials, Entospletinib demonstrates clinical activity in subjects with relapsed or refractory CLL with acceptable toxicity.


Chemical Structure

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Entospletinib
CAS# 1229208-44-9

Theoretical Analysis

MedKoo Cat#: 206107
Name: Entospletinib
CAS#: 1229208-44-9
Chemical Formula: C23H21N7O
Exact Mass: 411.18076
Molecular Weight: 411.46
Elemental Analysis: C, 67.14; H, 5.14; N, 23.83; O, 3.89

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Size Price Availability Quantity
10.0mg USD 150.0 Same day
25.0mg USD 250.0 Same day
50.0mg USD 450.0 Same day
100.0mg USD 750.0 Same day
200.0mg USD 1250.0 Same day
500.0mg USD 2850.0 Same day
1.0g USD 3950.0 Same day
2.0g USD 6550.0 Ready to ship
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Synonym: Entospletinib; GS9973; GS 9973; GS-9973.

IUPAC/Chemical Name: 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine

InChi Key: XSMSNFMDVXXHGJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H21N7O/c1-2-17-14-25-28-20(17)13-16(1)21-15-30-8-7-24-23(30)22(27-21)26-18-3-5-19(6-4-18)29-9-11-31-12-10-29/h1-8,13-15H,9-12H2,(H,25,28)(H,26,27)

SMILES Code: C12=NC=CN1C=C(C3=CC4=C(C=C3)C=NN4)N=C2NC5=CC=C(N6CCOCC6)C=C5

Appearance: 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: Entospletinib (GS-9973) is a Syk inhibitor with an IC50 of 7.7 nM.
In vitro activity: The effects of a Btk inhibitor, tirabrutinib, and a Syk inhibitor, entospletinib, were investigated alone and in combination on platelet signaling and functions in vitro. Entospletinib alone efficiently inhibited washed platelet aggregation in response to collagen. However, entospletinib only weakly affected platelet activation in platelet-rich plasma. Importantly, the combination of tirabrutinib and entospletinib induced a significant decrease in platelet response to collagen in vitro. Reference: J Thromb Haemost. 2020 Dec;18(12):3336-3351. https://onlinelibrary.wiley.com/doi/10.1111/jth.15098
In vivo activity: Potential utility of ENTO (Entospletinib) as GVHD (graft-versus-host disease) prophylaxis was examined using a preclinical mouse model of eye and skin GVHD and ENTO-compounded chow. Early SYK inhibition improved blood immune cell reconstitution in GVHD mice and prolonged survival, with 60% of mice surviving to day +120 compared with 10% of mice treated with placebo. Compared with mice receiving placebo, mice receiving ENTO had dramatic improvements in clinical eye scores, alopecia scores, and skin scores. Reference: JCI Insight. 2018 Oct 4;3(19):e122430. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237454/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 34.5 83.85
DMSO:PBS (pH 7.2) (1:2) 0.3 0.73

Preparing Stock Solutions

The following data is based on the product molecular weight 411.46 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. Series J, Ribes A, Garcia C, Souleyreau P, Bauters A, Morschhauser F, Jürgensmeier JM, Sié P, Ysebaert L, Payrastre B. Effects of novel Btk and Syk inhibitors on platelet functions alone and in combination in vitro and in vivo. J Thromb Haemost. 2020 Dec;18(12):3336-3351. doi: 10.1111/jth.15098. Epub 2020 Oct 26. PMID: 32926549. 2. Poe JC, Jia W, Di Paolo JA, Reyes NJ, Kim JY, Su H, Sundy JS, Cardones AR, Perez VL, Chen BJ, Chao NJ, Cardona DM, Saban DR, Sarantopoulos S. SYK inhibitor entospletinib prevents ocular and skin GVHD in mice. JCI Insight. 2018 Oct 4;3(19):e122430. doi: 10.1172/jci.insight.122430. PMID: 30282825; PMCID: PMC6237454.
In vitro protocol: 1. Series J, Ribes A, Garcia C, Souleyreau P, Bauters A, Morschhauser F, Jürgensmeier JM, Sié P, Ysebaert L, Payrastre B. Effects of novel Btk and Syk inhibitors on platelet functions alone and in combination in vitro and in vivo. J Thromb Haemost. 2020 Dec;18(12):3336-3351. doi: 10.1111/jth.15098. Epub 2020 Oct 26. PMID: 32926549.
In vivo protocol: 1. Poe JC, Jia W, Di Paolo JA, Reyes NJ, Kim JY, Su H, Sundy JS, Cardones AR, Perez VL, Chen BJ, Chao NJ, Cardona DM, Saban DR, Sarantopoulos S. SYK inhibitor entospletinib prevents ocular and skin GVHD in mice. JCI Insight. 2018 Oct 4;3(19):e122430. doi: 10.1172/jci.insight.122430. PMID: 30282825; PMCID: PMC6237454.

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1: Sharman J, Hawkins M, Kolibaba K, Boxer M, Klein L, Wu M, Hu J, Abella S, Yasenchak C. An open-label phase 2 trial of entospletinib (GS-9973), a selective  spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2015 Apr 9;125(15):2336-43. doi: 10.1182/blood-2014-08-595934. Epub 2015 Feb 18. PubMed PMID: 25696919; PubMed Central PMCID: PMC4401348.



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