ONO4059-Analog | CAS#1351635-67-0 | 1351636-18-4 | 1439901-97-9 |BTK inhibitor

ONO4059-Analog
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205914

CAS#: 1351635-67-0 (ONO-4059-analog)

Description: ONO4059-Analog, CAS#1351635-67-0, is a potent and selective BTK inhibitor, and is a structural analogue of ONO-4059. ONO4059 is currently under clinical trials. Note: ONO4059 HCl has CAS#1439901-97-9; ONO4059 free base has CAS#1351636-18-4.

Chemical Structure

ONO4059-Analog

CAS# 1351635-67-0 (ONO-4059-analog)

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205914
Name: ONO4059-Analog
CAS#: 1351635-67-0 (ONO-4059-analog)
Chemical Formula: C25H24N6O3
Exact Mass: 456.19
Molecular Weight: 456.506
Elemental Analysis: C, 65.78; H, 5.30; N, 18.41; O, 10.51

Price and Availability

Size	Price	Availability
5mg	USD 285	2 weeks
10mg	USD 450	2 weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: ONO4059-Analog; ONO 4059-Analog; ONO-4059-Analog; GS 4059-Analog; GS-4059-Analog; GS4059-Analog.

IUPAC/Chemical Name: (S)-9-(1-acryloylpiperidin-3-yl)-6-amino-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one

InChi Key: KSUDUUBCXJUFRL-SFHVURJKSA-N

InChi Code: InChI=1S/C25H24N6O3/c1-2-21(32)29-14-6-7-18(15-29)31-24-22(23(26)27-16-28-24)30(25(31)33)17-10-12-20(13-11-17)34-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m0/s1

SMILES Code: O=C1N(C2=CC=C(C=C2)OC3=CC=CC=C3)C4=C(N)N=CN=C4N1[C@@H]5CN(C(C=C)=O)CCC5

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, 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: Note: As of 5/19/2016, Sci-Finder listed ONO4059 has CAS#1351635-67-0. In a recent paper ( Blood. 2016 Jan 28;127(4):411-9.), ONO-4059 has 1351636-18-4 We consider the structure in paper (( Blood. 2016 Jan 28;127(4):411-9.) is more reliable. Thus we rename CAS#1351635-67-0 as ONO4059-analog

Product Data:

Product Data

Instruction:

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Biological target:	ONO-4059 analog is the analog of ONO-4059, ONO-4059 is a highly potent and selective Btk inhibitor.
In vitro activity:	In vitro kinase assays showed that, compared with ibrutinib, tirabrutinib and other second-generation BTK inhibitors demonstrated a highly selective kinase profile. Data from in vitro cellular systems showed that tirabrutinib selectively affected B-cells. Tirabrutinib inhibited the cell growth of both TMD8 and U-2932 cells in correlation with the inhibition of BTK autophosphorylation. Reference: PLoS One. 2023 Mar 10;18(3):e0282166. https://pubmed.ncbi.nlm.nih.gov/36897912/
In vivo activity:	The RANKL model studies show that tirabrutinib significantly suppressed bone loss with the inhibition of serum TRAPCP5b and urinary CTX-1. Bone Mineral Density (BMD) loss in tirabrutinib-treated mice was 55% (P < .05), 87% (P < .001) and 88% (P < .001) for the 3, 10 and 30 mg/kg dose groups respectively. Btk and Tec are required for osteoclast differentiation and activation based on the genetic evidence obtained from Btk and Tec double deficient mice. Tirabrutinib may be a novel therapeutic target for bone diseases, such as osteoporosis and RA. Reference: Bone Rep. 2019 Mar 15;10:100201. https://pubmed.ncbi.nlm.nih.gov/30956999/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	25.0	54.76
	DMF:PBS (pH 7.2) (1:1)	0.5	1.10
	DMSO	35.0	76.67

Preparing Stock Solutions

The following data is based on the product molecular weight 456.51 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. Kozaki R, Yasuhiro T, Kato H, Murai J, Hotta S, Ariza Y, Sakai S, Fujikawa R, Yoshida T. Investigation of the anti-tumor mechanism of tirabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, by phosphoproteomics and transcriptomics. PLoS One. 2023 Mar 10;18(3):e0282166. doi: 10.1371/journal.pone.0282166. PMID: 36897912; PMCID: PMC10004634. 2. Das S, Bar-Sagi D. BTK signaling drives CD1dhiCD5+ regulatory B-cell differentiation to promote pancreatic carcinogenesis. Oncogene. 2019 Apr;38(17):3316-3324. doi: 10.1038/s41388-018-0668-3. Epub 2019 Jan 11. PMID: 30635655; PMCID: PMC6486434. 3. Ariza Y, Murata M, Ueda Y, Yoshizawa T. Bruton's tyrosine kinase (Btk) inhibitor tirabrutinib suppresses osteoclastic bone resorption. Bone Rep. 2019 Mar 15;10:100201. doi: 10.1016/j.bonr.2019.100201. PMID: 30956999; PMCID: PMC6431727.
In vitro protocol:	1. Kozaki R, Yasuhiro T, Kato H, Murai J, Hotta S, Ariza Y, Sakai S, Fujikawa R, Yoshida T. Investigation of the anti-tumor mechanism of tirabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, by phosphoproteomics and transcriptomics. PLoS One. 2023 Mar 10;18(3):e0282166. doi: 10.1371/journal.pone.0282166. PMID: 36897912; PMCID: PMC10004634. 2. Das S, Bar-Sagi D. BTK signaling drives CD1dhiCD5+ regulatory B-cell differentiation to promote pancreatic carcinogenesis. Oncogene. 2019 Apr;38(17):3316-3324. doi: 10.1038/s41388-018-0668-3. Epub 2019 Jan 11. PMID: 30635655; PMCID: PMC6486434.
In vivo protocol:	1. Kozaki R, Yasuhiro T, Kato H, Murai J, Hotta S, Ariza Y, Sakai S, Fujikawa R, Yoshida T. Investigation of the anti-tumor mechanism of tirabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, by phosphoproteomics and transcriptomics. PLoS One. 2023 Mar 10;18(3):e0282166. doi: 10.1371/journal.pone.0282166. PMID: 36897912; PMCID: PMC10004634. 2. Ariza Y, Murata M, Ueda Y, Yoshizawa T. Bruton's tyrosine kinase (Btk) inhibitor tirabrutinib suppresses osteoclastic bone resorption. Bone Rep. 2019 Mar 15;10:100201. doi: 10.1016/j.bonr.2019.100201. PMID: 30956999; PMCID: PMC6431727.

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1: Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016 Mar 9;9:21. doi: 10.1186/s13045-016-0250-9. PubMed PMID: 26957112; PubMed Central PMCID: PMC4784459.

2: Walter HS, Rule SA, Dyer MJ, Karlin L, Jones C, Cazin B, Quittet P, Shah N, Hutchinson CV, Honda H, Duffy K, Birkett J, Jamieson V, Courtenay-Luck N, Yoshizawa T, Sharpe J, Ohno T, Abe S, Nishimura A, Cartron G, Morschhauser F, Fegan C, Salles G. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016 Jan 28;127(4):411-9. doi: 10.1182/blood-2015-08-664086. Epub 2015 Nov 5. PubMed PMID: 26542378; PubMed Central PMCID: PMC4731845.

3: Robak P, Smolewski P, Robak T. Emerging immunological drugs for chronic lymphocytic leukemia. Expert Opin Emerg Drugs. 2015 Sep;20(3):423-47. doi: 10.1517/14728214.2015.1046432. Epub 2015 Jul 11. Review. PubMed PMID: 26153226.

4: 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. Review. PubMed PMID: 24357428.

4: Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013 Aug 19;6:59. doi: 10.1186/1756-8722-6-59. Review. PubMed PMID: 23958373; PubMed Central PMCID: PMC3751776.

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ONO4059-Analog featured