Spebrutinib |AVL-292 | CC-292 | CAS#1202757-89-8 | BTK inhibitor

MedKoo Cat#: 204480 | Name: Spebrutinib

Description:

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

Spebrutinib, also known as AVL-292 or CC-292, is an orally bioavailable, selective inhibitor of BrutonÂ’s agammaglobulinemia tyrosine kinase (BTK), with potential antineoplastic activity. Upon administration, AVL-292 targets and covalently binds to BTK, thereby preventing its activity. By irreversibly inhibiting BTK, administration of this agent may lead to an inhibition of B cell receptor (BCR) signaling and may inhibit cell proliferation of B-cell malignancies.

Chemical Structure

Spebrutinib

CAS#1202757-89-8 (free base)

Theoretical Analysis

MedKoo Cat#: 204480

Name: Spebrutinib

CAS#: 1202757-89-8 (free base)

Chemical Formula: C22H22FN5O3

Exact Mass: 423.1707

Molecular Weight: 423.44

Elemental Analysis: C, 62.40; H, 5.24; F, 4.49; N, 16.54; O, 11.34

Price and Availability

Size	Price	Availability
25mg	USD 90.00	Ready to ship
50mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 850.00	Ready to ship
1g	USD 1,450.00	Ready to ship
2g	USD 2,450.00	Ready to ship
5g	USD 4,650.00	Ready to ship

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Related CAS #

1360053-81-1 (besylate) 1202757-89-8 (free base)

Synonym

CC292; CC-292; CC 292; AVL292; AVL-292; AVL 292; Spebrutinib.

IUPAC/Chemical Name

N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide

InChi Key

KXBDTLQSDKGAEB-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H22FN5O3/c1-3-20(29)25-16-5-4-6-17(13-16)26-21-19(23)14-24-22(28-21)27-15-7-9-18(10-8-15)31-12-11-30-2/h3-10,13-14H,1,11-12H2,2H3,(H,25,29)(H2,24,26,27,28)

SMILES Code

C=CC(NC1=CC=CC(NC2=NC(NC3=CC=C(OCCOC)C=C3)=NC=C2F)=C1)=O

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

More Info

AVL-292 has demonstrated efficacy in animal models of rheumatoid arthritis and multiple sclerosis, diseases in which B cells play an important role. Btk plays a critical role in the development and activation of B cells, and its inhibition will be of therapeutic significance in the treatment of both of B cell-related hematological cancers (e.g. non-Hodgkin lymphoma (NHL) and B cell chronic lymphocytic leukemia (B-CLL), and autoimmune diseases (e.g. rheumatoid arthritis). (source: http://www.avilatx.com/pipeline/bruton%27s-tyrosine-kinase-inhibitor-program.html).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC31129

View CoA: current batch, Lot#BBC40410

QC Data

View QC data: current batch, Lot#BBC31129

View QC data: current batch, Lot#BBC40410

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Spebrutinib is a covalent inhibitor of Btk with IC50 value of 0.5 nM.

In vitro activity:

Spebrutinib showed a cytostatic effect in a subset of cell lines, with REC-1, MINO, and UPN-1 being the most sensitive, while MAVER-1 and Z138 were the most resistant to spebrutinib, similar to ibrutinib. Marginal apoptosis (10–15%) was observed in the most sensitive cell lines (UPN-1 and REC-1). Spebrutinib reduced both constitutive and IgM-induced BTK phosphorylation at the Y223 residue in MCL cell lines and primary cells, regardless of their sensitivity to the inhibitor. Reference: Haematologica. 2017 Nov; 102(11): e447–e451. https://pubmed.ncbi.nlm.nih.gov/28838994/

In vivo activity:

Spebrutinib is a specific BTK inhibitor with promising performance in combination with bendamustine in chronic lymphocytic leukemia (CLL). In a mouse model of CLL, spebrutinib reduced tumor load and normalized tumor-associated expansion of T cells and monocytes, while not affecting T cell function. The combination of spebrutinib and bendamustine impaired CLL cell proliferation in vivo and enhanced the control of CLL progression. Reference: Int J Cancer. 2019 Jun 1;144(11):2762-2773. https://pubmed.ncbi.nlm.nih.gov/30468254/

	Solvent	mg/mL	mM
Solubility
	Ethanol	0.5	1.18
	DMSO:PBS (pH 7.2) (1:30)	0.0	0.07
	Ethanol	0.5	1.18

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 423.44 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. Vidal-Crespo A, Rodriguez V, Matas-Cespedes A, Lee E, Rivas-Delgado A, Giné E, Navarro A, Beà S, Campo E, López-Guillermo A, Lopez-Guerra M, Roué G, Colomer D, Pérez-Galán P. The Bruton tyrosine kinase inhibitor CC-292 shows activity in mantle cell lymphoma and synergizes with lenalidomide and NIK inhibitors depending on nuclear factor-κB mutational status. Haematologica. 2017 Nov;102(11):e447-e451. doi: 10.3324/haematol.2017.168930. Epub 2017 Aug 24. PMID: 28838994; PMCID: PMC5664406. 2. Arnason JE, Brown JR. B cell receptor pathway in chronic lymphocytic leukemia: specific role of CC-292. Immunotargets Ther. 2014 Jan 24;3:29-38. doi: 10.2147/ITT.S37419. PMID: 27471698; PMCID: PMC4918232. 3. Lee-Vergés E, Hanna BS, Yazdanparast H, Rodríguez V, Rodríguez ML, Giró A, Vidal-Crespo A, Rosich L, Amador V, Aymerich M, Villamor N, Delgado J, Lichter P, Pérez-Galán P, López-Guerra M, Campo E, Seiffert M, Colomer D. Selective BTK inhibition improves bendamustine therapy response and normalizes immune effector functions in chronic lymphocytic leukemia. Int J Cancer. 2019 Jun 1;144(11):2762-2773. doi: 10.1002/ijc.32010. Epub 2019 Jan 16. PMID: 30468254. 4. Daryaee F, Zhang Z, Gogarty KR, Li Y, Merino J, Fisher SL, Tonge PJ. A quantitative mechanistic PK/PD model directly connects Btk target engagement and in vivo efficacy. Chem Sci. 2017 May 1;8(5):3434-3443. doi: 10.1039/c6sc03306g. Epub 2017 Mar 14. PMID: 28507715; PMCID: PMC5417014.

In vitro protocol:

In vivo protocol:

1. Lee-Vergés E, Hanna BS, Yazdanparast H, Rodríguez V, Rodríguez ML, Giró A, Vidal-Crespo A, Rosich L, Amador V, Aymerich M, Villamor N, Delgado J, Lichter P, Pérez-Galán P, López-Guerra M, Campo E, Seiffert M, Colomer D. Selective BTK inhibition improves bendamustine therapy response and normalizes immune effector functions in chronic lymphocytic leukemia. Int J Cancer. 2019 Jun 1;144(11):2762-2773. doi: 10.1002/ijc.32010. Epub 2019 Jan 16. PMID: 30468254. 2. Daryaee F, Zhang Z, Gogarty KR, Li Y, Merino J, Fisher SL, Tonge PJ. A quantitative mechanistic PK/PD model directly connects Btk target engagement and in vivo efficacy. Chem Sci. 2017 May 1;8(5):3434-3443. doi: 10.1039/c6sc03306g. Epub 2017 Mar 14. PMID: 28507715; PMCID: PMC5417014.

1: Burger JA. Bruton's tyrosine kinase (BTK) inhibitors in clinical trials. Curr Hematol Malig Rep. 2014 Mar;9(1):44-9. doi: 10.1007/s11899-013-0188-8. PubMed PMID: 24357428.