Momelotinib

Last updated

Contents

Momelotinib
Momelotinib.svg
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
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
PubChem CID
UNII
  • 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
  • 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
C23H22N6O2
Molar mass 414.469 g·mol−1
Pharmacology
L01EJ04 ( WHO )
By mouth
Legal status
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Momelotinib
Clinical data
Other namesMomelotinib hydrochloride hydrate (JAN JP), Momelotinib dihydrochloride (USAN US)
License data
Identifiers
PDB ligand
CompTox Dashboard (EPA)

Momelotinib, sold under the brand name Ojjaara, 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] It was approved in the EU in January 2024. [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

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] The EU gave approval for Omjjara in January 2024. [9]

Related Research Articles

Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 and 2, but were ultimately published as "Janus kinase". The name is taken from the two-faced Roman god of beginnings, endings and duality, Janus, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first.

Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. In PMF, the bony aspects of bone marrow are remodeled in a process called osteosclerosis; in addition, fibroblast secrete collagen and reticulin proteins that are collectively referred to as (fibrosis). These two pathological processes compromise the normal function of bone marrow resulting in decreased production of blood cells such as erythrocytes, granulocytes and megakaryocytes, the latter cells responsible for the production of platelets.

<span class="mw-page-title-main">Lestaurtinib</span> Chemical compound

Lestaurtinib is a tyrosine kinase inhibitor structurally related to staurosporine. This semisynthetic derivative of the indolocarbazole K252a was investigated by Cephalon as a treatment for various types of cancer. It is an inhibitor of the kinases fms-like tyrosine kinase 3 (FLT3), Janus kinase 2 (JAK2), tropomyosin receptor kinase (trk) A (TrkA), TrkB and TrkC.

A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, is a type of immune modulating medication, which inhibits the activity of one or more of the Janus kinase family of enzymes, thereby interfering with the JAK-STAT signaling pathway in lymphocytes.

Givinostat, sold under the brand name Duvyzat is a medication used for the treatment of Duchenne muscular dystrophy. It is a histone deacetylase inhibitor with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities. It is a histone deacetylase (HDAC) inhibitor that works by targeting pathogenic processes to reduce inflammation and loss of muscle.

<span class="mw-page-title-main">Ruxolitinib</span> Medication

Ruxolitinib, sold under the brand name Jakafi among others, is a medication used for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative neoplasm that affects the bone marrow; polycythemia vera, when there has been an inadequate response to or intolerance of hydroxyurea; and steroid-refractory acute graft-versus-host disease. Ruxolitinib is a Janus kinase inhibitor. It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi.

<span class="mw-page-title-main">Fedratinib</span> Chemical compound

Fedratinib, sold under the brand name Inrebic, is an anti-cancer medication used to treat myeloproliferative diseases including myelofibrosis. It is used in the form of fedratinib hydrochloride capsules that are taken by mouth. It is a semi-selective inhibitor of Janus kinase 2 (JAK-2). It was approved by the FDA on 16 August 2019.

<span class="mw-page-title-main">Baricitinib</span> Chemical compound

Baricitinib, sold under the brand name Olumiant among others, is an immunomodulatory medication used for the treatment of rheumatoid arthritis, alopecia areata, and COVID-19. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.

<span class="mw-page-title-main">Trametinib</span> Anticancer medication

Trametinib, sold under the brand name Mekinist among others, is an anticancer medication used for the treatment of melanoma and glioma. It is a MEK inhibitor drug with anti-cancer activity. It inhibits MEK1 and MEK2. It is taken by mouth.

<span class="mw-page-title-main">Pacritinib</span> Medication used to treat myelofibrosis

Pacritinib, sold under the brand name Vonjo, is an anti-cancer medication used to treat myelofibrosis. It is a macrocyclic protein kinase inhibitor. It mainly inhibits Janus kinase 2 (JAK2) and Fms-like tyrosine kinase 3\CD135 (FLT3).

<span class="mw-page-title-main">Filgotinib</span> Chemical compound

Filgotinib, sold under the brand name Jyseleca, is a medication used for the treatment of rheumatoid arthritis (RA). It was developed by the Belgian-Dutch biotech company Galapagos NV.

<span class="mw-page-title-main">Acalabrutinib</span> Chemical compound

Acalabrutinib, sold under the brand name Calquence, is a medication used to treat various types of non-Hodgkin lymphoma, including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic Lymphoma (CLL/SLL). It may be used both in relapsed as well as in treatment-naive settings.

<span class="mw-page-title-main">Oclacitinib</span> Medication

Oclacitinib, sold under the brand name Apoquel among others, is a veterinary medication used in the control of atopic dermatitis and pruritus from allergic dermatitis in dogs at least 12 months of age. Chemically, it is a synthetic cyclohexylamino pyrrolopyrimidine janus kinase inhibitor that is relatively selective for JAK1. It inhibits signal transduction when the JAK is activated and thus helps downregulate expression of inflammatory cytokines.

<span class="mw-page-title-main">Upadacitinib</span> Chemical compound (medication)

Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

<span class="mw-page-title-main">Janus kinase 3 inhibitor</span>

Janus kinase 3 inhibitors, also called JAK3 inhibitors, are a new class of immunomodulatory agents that inhibit Janus kinase 3. They are used for the treatment of autoimmune diseases. The Janus kinases are a family of four nonreceptor tyrosine-protein kinases, JAK1, JAK2, JAK3, and TYK2. They signal via the JAK/STAT pathway, which is important in regulating the immune system. Expression of JAK3 is largely restricted to lymphocytes, while the others are ubiquitously expressed, so selective targeting of JAK3 over the other JAK isozymes is attractive as a possible treatment of autoimmune diseases.

<span class="mw-page-title-main">Abrocitinib</span> Chemical compound

Abrocitinib, sold under the brand name Cibinqo, is a medication used for the treatment of atopic dermatitis (eczema). It is a Janus kinase inhibitor and it was developed by Pfizer. It is taken by mouth.

<span class="mw-page-title-main">Zotiraciclib</span> Chemical compound

Zotiraciclib (TG02) is a potent oral spectrum selective kinase inhibitor for the treatment of cancer. It was discovered in Singapore by S*BIO Pte Ltd and falls under the category of small molecule macrocycles. It crosses the blood brain barrier and acts by depleting Myc through the inhibition of cyclin-dependent kinase 9 (CDK9). It is one of a number of CDK inhibitors under investigation; others targeting CDK9 for the treatment of acute myeloid leukemia include alvocidib and atuveciclib. Myc overexpression is a known factor in many cancers, with 80 percent of glioblastomas characterized by this property. Zotiraciclib has been granted orphan drug designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of gliomas.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

<span class="mw-page-title-main">Mitapivat</span> Chemical compound

Mitapivat, sold under the brand name Pyrukynd, is a medication used to treat hemolytic anemia. It is taken as the sulfate hydrate salt by mouth. Mitapivat is a pyruvate kinase activator.

<span class="mw-page-title-main">Deucravacitinib</span> Chemical compound

Deucravacitinib, sold under the brand name Sotyktu, is a medication used for the treatment of moderate-to-severe plaque psoriasis. It is a tyrosine kinase 2 (TYK2) inhibitor and it is taken by mouth. It was developed by Bristol Myers Squibb.

References

  1. 1 2 3 4 5 "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.
  2. "Omjjara EPAR". European Medicines Agency. 5 August 2011. Retrieved 18 March 2024.
  3. "Omjjara Product information". Union Register of medicinal products. 26 January 2024. Retrieved 18 March 2024.
  4. 1 2 3 "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.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. 1 2 "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.PD-icon.svg 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.
  8. 1 2 "Omjjara: Pending EC decision". European Medicines Agency (EMA). 10 November 2023. Archived from the original on 29 November 2023. Retrieved 5 December 2023.
  9. "GSK's Omjjara Authorized in EU for Treating Myelofibrosis With Anemia". MarketWatch. Retrieved 30 January 2024.