Momelotinib

Momelotinib
Clinical data
Other names	Momelotinib hydrochloride hydrate (JAN JP), Momelotinib dihydrochloride (USAN US)
License data	US DailyMed: Momelotinib;
Identifiers
PDB ligand	C87 (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID801026049 ;

Momelotinib
Names
	Preferred IUPAC name N-(Cyanomethyl)-4-{2-[4-(morpholin-4-yl)anilino]pyrimidin-4-yl}benzamide
	Other names CYT-387; CYT-11387; GS-0387; Ojjaara; Omjjara;
Identifiers
CAS Number	1056634-68-4; as dihydrochloride: 1380317-28-1; 1841094-17-4;
3D model (JSmol)	Interactive image; as dihydrochloride: Interactive image;
ChEBI	CHEBI:91407;
ChEMBL	ChEMBL1078178;
ChemSpider	24676202;
DrugBank	DB11763; as dihydrochloride: DBSALT003445;
IUPHAR/BPS	7791;
KEGG	D10315; as dihydrochloride: D10358; D10889;
PubChem CID	25062766;
UNII	6O01GMS00P; as dihydrochloride: RBH995N496; LDX8893L5D;
CompTox Dashboard (EPA)	DTXSID801026049 ;
	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; as dihydrochloride: Cl.Cl.O=C(NCC#N)C1=CC=C(C=C1)C1=NC(NC2=CC=C(C=C2)N2CCOCC2)=NC=C1;
Properties
Chemical formula	C23H22N6O2
Molar mass	414.469 g·mol−1
Pharmacology
ATC code	L01EJ04 (WHO)
Routes of; administration	By mouth
Legal status	US: ℞-only; EU: Rx-only;
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Momelotinib, sold under the brand name Ojjaara among others, is an anticancer medication used for the treatment of myelofibrosis.^[1] It is a Janus kinase inhibitor and it is taken by mouth.^[1]

The most common adverse reactions include dizziness, fatigue, bacterial infection, hemorrhage, thrombocytopenia, diarrhea, and nausea.^[4]

Momelotinib was approved for medical use in the United States in September 2023,^[1]^[4]^[5] and in the European Union in January 2024.^[2]^[6]

Medical uses

Momelotinib is indicated for the treatment of intermediate or high-risk myelofibrosis in adults with anemia.^[1]^[4]^[5]

Pharmacology

Pharmacodynamics

It 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).^[7]

Society and culture

Legal status

In November 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Omjjara, intended for the treatment of disease-related splenomegaly or symptoms in adults with moderate-to-severe anemia who have primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis.^[8] The applicant for this medicinal product is Glaxosmithkline Trading Services Limited.^[8] Momelotinib was approved for medical use in the European Union in January 2024.^[2]^[3]

References

^ ^a ^b ^c ^d ^e "Ojjaara- momelotinib tablet". DailyMed. U.S. National Library of Medicine. 15 September 2023. Archived from the original on 30 November 2023. Retrieved 20 September 2023.
^ ^a ^b ^c "Omjjara EPAR". European Medicines Agency. 5 August 2011. Retrieved 18 March 2024.
^ ^a ^b "Omjjara Product information". Union Register of medicinal products. 26 January 2024. Retrieved 18 March 2024.
^ ^a ^b ^c "FDA Roundup: September 19, 2023". U.S. Food and Drug Administration (FDA) (Press release). 19 September 2023. Archived from the original on 21 September 2023. Retrieved 20 September 2023. This article incorporates text from this source, which is in the public domain.
^ ^a ^b "Novel Drug Approvals for 2023". U.S. Food and Drug Administration (FDA). 15 September 2023. Archived from the original on 21 January 2023. Retrieved 20 September 2023. This article incorporates text from this source, which is in the public domain.
^ "GSK's Omjjara Authorized in EU for Treating Myelofibrosis With Anemia". MarketWatch. Retrieved 30 January 2024.
^ 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". Leukemia. 23 (8): 1441–1445. doi:10.1038/leu.2009.50. PMID 19295546. S2CID 26947444.
^ ^a ^b "Omjjara: Pending EC decision". European Medicines Agency (EMA). 10 November 2023. Archived from the original on 29 November 2023. Retrieved 5 December 2023.

External links

Clinical trial number NCT04173494 for "A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Patients (MOMENTUM)" at ClinicalTrials.gov
Clinical trial number NCT01969838 for "Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis (Simplify 1)" at ClinicalTrials.gov

[Ojjaara_FDA_label-1] "Ojjaara- momelotinib tablet". DailyMed. U.S. National Library of Medicine. 15 September 2023. Archived from the original on 30 November 2023. Retrieved 20 September 2023.

[Omjjara_EPAR-2] "Omjjara EPAR". European Medicines Agency. 5 August 2011. Retrieved 18 March 2024.

[Omjjara_Product_information-3] "Omjjara Product information". Union Register of medicinal products. 26 January 2024. Retrieved 18 March 2024.

[FDA_PR_20230918-4] "FDA Roundup: September 19, 2023". U.S. Food and Drug Administration (FDA) (Press release). 19 September 2023. Archived from the original on 21 September 2023. Retrieved 20 September 2023. This article incorporates text from this source, which is in the public domain.

[Novel_Drug_Approvals_for_2023-5] "Novel Drug Approvals for 2023". U.S. Food and Drug Administration (FDA). 15 September 2023. Archived from the original on 21 January 2023. Retrieved 20 September 2023. This article incorporates text from this source, which is in the public domain.

[6] "GSK's Omjjara Authorized in EU for Treating Myelofibrosis With Anemia". MarketWatch. Retrieved 30 January 2024.

[7] 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". Leukemia. 23 (8): 1441–1445. doi:10.1038/leu.2009.50. PMID 19295546. S2CID 26947444.

[Omjjara:_Pending_EC_decision-8] "Omjjara: Pending EC decision". European Medicines Agency (EMA). 10 November 2023. Archived from the original on 29 November 2023. Retrieved 5 December 2023.

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