Momelotinib

Momelotinib
Names
	IUPAC name N-(cyanomethyl)-4-{2-[4-(morpholin-4-yl)anilino]pyrimidin-4-yl}benzamide
	Other names CYT-387, CYT-11387, GS-0387
Identifiers
CAS Number	1056634-68-4;
3D model (JSmol)	Interactive image;
ChemSpider	24676202;
IUPHAR/BPS	7791;
KEGG	D10315;
PubChem CID	25062766;
UNII	6O01GMS00P ;
	InChI InChI=1S/C23H22N6O2/c24-10-12-25-22(30)18-3-1-17(2-4-18)21-9-11-26-23(28-21)27-19-5-7-20(8-6-19)29-13-15-31-16-14-29/h1-9,11H,12-16H2,(H,25,30)(H,26,27,28) Key: ZVHNDZWQTBEVRY-UHFFFAOYSA-N;
	SMILES c1cc(ccc1c2ccnc(n2)Nc3ccc(cc3)N4CCOCC4)C(=O)NCC#N;
Properties
Chemical formula	C23H22N6O2
Molar mass	414.47 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	Infobox references

Momelotinib (INN,^[1] formerly GS-0387, CYT-387) is an inhibitor of Janus kinases JAK1 and JAK2, acting as an ATP competitor with IC₅₀ values of 11 and 18 nM, respectively. The inhibitor is significantly less active towards other kinases, including JAK3 (IC₅₀ = 0.16 μM).^[2]

As of 2011, momelotinib is being developed as a drug for myelofibrosis and currently undergoes Phase I/II clinical trials. Additional potential treatment indications for momelotinib include other myeloproliferative neoplasms, cancer (solid and liquid tumors) and inflammatory conditions.^[3]

As of 2016, momelotinib is being investigated for primary myelofibrosis or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF),^[4] as well as a treatment for relapsed or refractory metastatic pancreatic ductal adenocarcinoma (in combination with capecitabine and oxaliplatin).^[5]

Discovery

The drug was originally discovered by Australian drug discovery company Cytopia, then developed by YM BioSciences Inc. (since acquired by Gilead Sciences as of 2013).

References

↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed International Nonproprietary Names: List 107" (PDF). World Health Organization. p. 189. Retrieved 16 July 2016.
↑ Pardanani, A; Lasho, T; Smith, G; Burns, CJ; Fantino, E; Tefferi, A (August 2009). "CYT387, a Selective JAK1/JAK2 Inhibitor: in vitro Assessment of Kinase Selectivity and Preclinical Studies Using Cell Lines and Primary Cells from Polycythemia vera Patients" (PDF). Leukemia. 23 (8): 1441–5. doi:10.1038/leu.2009.50. PMID 19295546. Retrieved 16 July 2016.
↑ Pardanani, A; Vannucchi, AM; Passamonti, F; Cervantes, F; Barbui, T; Tefferi, A (February 2011). "JAK Inhibitor Therapy for Myelofibrosis: Critical Assessment of Value and Limitations" (PDF). Leukemia. 25 (2): 218–25. doi:10.1038/leu.2010.269. PMID 21079613. Retrieved 16 July 2016.
↑ "Momelotinib in Transfusion-Dependent Adults with Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)". ClinicalTrials.gov. Retrieved 16 July 2016.
↑ "Momelotinib Combined with Capecitabine and Oxaliplatin in Adults with Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma". ClinicalTrials.gov. Retrieved 16 July 2016.

External links

www.ymbiosciences.com

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[1] "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed International Nonproprietary Names: List 107" (PDF). World Health Organization. p. 189. Retrieved 16 July 2016.

[2] Pardanani, A; Lasho, T; Smith, G; Burns, CJ; Fantino, E; Tefferi, A (August 2009). "CYT387, a Selective JAK1/JAK2 Inhibitor: in vitro Assessment of Kinase Selectivity and Preclinical Studies Using Cell Lines and Primary Cells from Polycythemia vera Patients" (PDF). Leukemia. 23 (8): 1441–5. doi:10.1038/leu.2009.50. PMID 19295546. Retrieved 16 July 2016.

[3] Pardanani, A; Vannucchi, AM; Passamonti, F; Cervantes, F; Barbui, T; Tefferi, A (February 2011). "JAK Inhibitor Therapy for Myelofibrosis: Critical Assessment of Value and Limitations" (PDF). Leukemia. 25 (2): 218–25. doi:10.1038/leu.2010.269. PMID 21079613. Retrieved 16 July 2016.

[4] "Momelotinib in Transfusion-Dependent Adults with Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)". ClinicalTrials.gov. Retrieved 16 July 2016.

[5] "Momelotinib Combined with Capecitabine and Oxaliplatin in Adults with Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma". ClinicalTrials.gov. Retrieved 16 July 2016.