Nemiralisib | CAS# 1254036-71-9 | PI3Kδ Inhibitor

MedKoo Cat#: 565193 | Name: Nemiralisib

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Description:

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

Nemiralisib, also known as GSK2269557, is a highly potent and selective inhaled PI3Kδ inhibitor for the treatment of COPD.

Chemical Structure

Nemiralisib

CAS#1254036-71-9 (free base)

Theoretical Analysis

MedKoo Cat#: 565193

Name: Nemiralisib

CAS#: 1254036-71-9 (free base)

Chemical Formula: C26H28N6O

Exact Mass: 440.2325

Molecular Weight: 440.55

Elemental Analysis: C, 70.89; H, 6.41; N, 19.08; O, 3.63

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 325.00
10mg	USD 520.00
25mg	USD 940.00

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Related CAS #

1254036-77-5 (HCl) 1254036-71-9 (free base)

Synonym

GSK2269557; GSK-2269557; GSK 2269557; Nemiralisib

IUPAC/Chemical Name

2-[6-(1H-Indol-4-yl)-1H-indazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole

InChi Key

MCIDWGZGWVSZMK-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H28N6O/c1-17(2)32-10-8-31(9-11-32)16-19-14-28-26(33-19)22-12-18(13-25-23(22)15-29-30-25)20-4-3-5-24-21(20)6-7-27-24/h3-7,12-15,17,27H,8-11,16H2,1-2H3,(H,29,30)

SMILES Code

CC(N1CCN(CC2=CN=C(C3=CC(C4=CC=CC5=C4C=CN5)=CC6=C3C=NN6)O2)CC1)C

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

>3 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

Product Data

Instruction

View handling instruction

Biological target:

Nemiralisib (GSK2269557 free base) is a potent and highly selective PI3Kδ inhibitor with a pKi of 9.9.

In vitro activity:

Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation. Reference: J Med Chem. 2015 Sep 24;58(18):7381-99. https://pubmed.ncbi.nlm.nih.gov/26301626/

In vivo activity:

	Solvent	mg/mL	mM
Solubility
	DMSO	60.7	137.70
	Ethanol	8.0	18.16

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 440.55 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:

Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL, Jones P, Keeling SE, Le J, Livia S, Lucas F, Lunniss CJ, Parr NJ, Robinson E, Rowland P, Smith S, Thomas DA, Vitulli G, Washio Y, Hamblin JN. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem. 2015 Sep 24;58(18):7381-99. doi: 10.1021/acs.jmedchem.5b00767. Epub 2015 Sep 3. PMID: 26301626.

In vitro protocol:

In vivo protocol:

1: Begg M, Edwards CD, Hamblin JN, Pifani E, Wilson R, Gilbert J, Vitulli G, Mallett D, Morrell J, Hingle MI, Uddin S, Ehtesham F, Marotti M, Harell A, Newman C, Fernando D, Clark J, Cahn A, Hessel EM. Translation of inhaled drug optimization strategies into clinical pharmacokinetics and pharmacodynamics using GSK2292767A, a novel inhaled PI3Kδ inhibitor. J Pharmacol Exp Ther. 2019 Apr 2. pii: jpet.119.257311. doi: 10.1124/jpet.119.257311. [Epub ahead of print] PubMed PMID: 30940692. 2: Begg M, Wilson R, Hamblin JN, Montembault M, Green J, Deans A, Amour A, Worsley S, Fantom K, Cui Y, Dear G, Ahmad S, Kielkowska A, Clark J, Boyce M, Cahn A, Hessel EM. Relationship between pharmacokinetics and pharmacodynamic responses in healthy smokers informs a once daily dosing regimen for nemiralisib. J Pharmacol Exp Ther. 2019 Mar 18. pii: jpet.118.255109. doi: 10.1124/jpet.118.255109. [Epub ahead of print] PubMed PMID: 30886125. 3: Ino H, Wilson R, Terao T, Ogura H, Igarashi H, Cahn A, Numachi Y. Evaluation of the Safety, Tolerability, and Pharmacokinetics of GSK2269557 (Nemiralisib) Administered Via Dry Powder Inhaler to Healthy Japanese Subjects. Clin Pharmacol Drug Dev. 2019 Jan;8(1):78-86. doi: 10.1002/cpdd.614. Epub 2018 Oct 10. PubMed PMID: 30303626. 4: Khindri S, Cahn A, Begg M, Montembault M, Leemereise C, Cui Y, Hogg A, Wajdner H, Yang S, Robertson J, Hamblin JN, Ludwig-Sengpiel A, Kornmann O, Hessel EM. A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Investigate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Repeat Doses of Inhaled Nemiralisib in Adults with Persistent, Uncontrolled Asthma. J Pharmacol Exp Ther. 2018 Dec;367(3):405-413. doi: 10.1124/jpet.118.249516. Epub 2018 Sep 14. PubMed PMID: 30217958. 5: Wilson R, Jarvis E, Montembault M, Hamblin JN, Hessel EM, Cahn A. Safety, Tolerability, and Pharmacokinetics of Single and Repeat Doses of Nemiralisib Administered via the Ellipta Dry Powder Inhaler to Healthy Subjects. Clin Ther. 2018 Aug;40(8):1410-1417. doi: 10.1016/j.clinthera.2018.06.011. Epub 2018 Jul 25. PubMed PMID: 30055824.