RXT

(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

Created: 2014-07-31
Last modified:  2021-03-01

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Chemical Details

Formal Charge0
Atom Count41
Chiral Atom Count1
Bond Count44
Aromatic Bond Count15
2D diagram of RXT
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Chemical Component Summary

Name(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile
SynonymsRuxolitinib
Systematic Name (OpenEye OEToolkits)(3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile
FormulaC17 H18 N6
Molecular Weight306.365
TypeNON-POLYMER

Chemical Descriptors

TypeProgram Version Descriptor
SMILESACDLabs12.01N#CCC(n1ncc(c1)c3ncnc2c3ccn2)C4CCCC4
SMILESCACTVS3.385N#CC[CH](C1CCCC1)n2cc(cn2)c3ncnc4[nH]ccc34
SMILESOpenEye OEToolkits1.9.2c1c[nH]c2c1c(ncn2)c3cnn(c3)C(CC#N)C4CCCC4
Canonical SMILESCACTVS3.385 N#CC[C@H](C1CCCC1)n2cc(cn2)c3ncnc4[nH]ccc34
Canonical SMILESOpenEye OEToolkits1.9.2 c1c[nH]c2c1c(ncn2)c3cnn(c3)[C@H](CC#N)C4CCCC4
InChIInChI1.03 InChI=1S/C17H18N6/c18-7-5-15(12-3-1-2-4-12)23-10-13(9-22-23)16-14-6-8-19-17(14)21-11-20-16/h6,8-12,15H,1-5H2,(H,19,20,21)/t15-/m1/s1
InChIKeyInChI1.03 HFNKQEVNSGCOJV-OAHLLOKOSA-N

Drug Info: DrugBank

DrugBank IDDB08877 
NameRuxolitinib
Groups approved
DescriptionRuxolitinib, formerly known as INCB018424 or INC424, is an anticancer drug and a Janus kinase (JAK) inhibitor. It is a potent and selective inhibitor of JAK1 and JAK2,[A229698] which are tyrosine kinases involved in cytokine signalling and hematopoiesis.[A7450] Myeloproliferative neoplasms, such as myelofibrosis and polycythemia vera, are often characterized by aberrant activation of the JAK-STAT pathway, leading to abnormal blood cell counts and thrombotic complications. By inhibiting JAK1 and JAK2, ruxolitinib works to block the dysregulated cell signalling pathways and prevents abnormal blood cell proliferation.[A229708] Due to a large number of patients with myeloproliferative neoplasms who have JAK2 mutations, ruxolitinib was the first ATP-competitive inhibitor of JAK1 and JAK2 ever developed.[A229938] Ruxolitinib was first approved for the treatment of adult patients with myelofibrosis by the FDA in 2011, followed by EMA's approval in 2012.[A229708] In 2014, it was approved for the treatment of polycythemia vera in adults who have an inadequate response to or are intolerant of [hydroxyurea] and in 2019, ruxolitinib was approved for use in steroid-refractory acute graft-versus-host disease in adults and children.[L31958] The topical formulation of ruxolitinib is used to treat atopic dermatitis and vitiligo.[L39125] It is being investigated for other inflammatory skin conditions.[A229883] Ruxolitinib has been investigated to treat patients with coronavirus disease 2019 (COVID-19) accompanied by severe systemic hyperinflammation. In phase II clinical trials, ruxolitinib improved chest computed tomography and improved recovery in patients with lymphopenia.[A229713, A229718] However, phase III clinical trials later determined that ruxolitinib was inadequate in meeting its primary endpoint of reducing the number of hospitalized COVID-19 patients who experienced severe complications [L31968] thus the drug was not approved as a treatment for COVID-19.
Synonyms
  • Ruxolitinib
  • Recilisib sodium
  • Ruxolitinib phosphate
Brand Names
  • Jakavi
  • Jakafi
  • Opzelura
IndicationRuxolitinib is indicated for the treatment of the following conditions: - intermediate or high-risk myelofibrosis (MF), including prima1y MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults.[L31938] It is also used to treat disease-related splenomegaly or symptoms in adult patients with these conditions.[L32073] - polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.[L31938] - steroid-refracto1y acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older.[L31938] - chronic GVHD in patients aged 12 years and older who have failed one or two lines of systemic therapy.[L31938] Topical ruxolitinib is indicated for: - the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised patients patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.[L39125] - the treatment of non-segmental vitiligo in adult and pediatric patients 12 years of age and older.[L39125, L46068]
Categories
  • Agents for Dermatitis, Excluding Corticosteroids
  • Antineoplastic Agents
  • Antineoplastic and Immunomodulating Agents
  • Cancer immunotherapy
  • Cytochrome P-450 CYP2C9 Substrates
ATC-Code
  • D11AH09
  • L01EJ01
CAS number941678-49-5

Drug Targets

NameTarget SequencePharmacological ActionActions
Tyrosine-protein kinase JAK2MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKS...unknowninhibitor
Tyrosine-protein kinase JAK1MQYLNIKEDCNAMAFCAKMRSSKKTEVNLEAPEPGVEVIFYLSDREPLRL...unknowninhibitor
Tyrosine-protein kinase JAK3MAPPSEETPLIPQRSCSLLSTEAGALHVLLPARGPGPPQRLSFSFGDHLA...unknowninhibitor
Non-receptor tyrosine-protein kinase TYK2MPLRHWGMARGSKPVGDGAQPMAAMGGLKVLLHWAGPGGGEPWVTFSESS...unknowninhibitor
Cytochrome P450 3A4MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...unknownsubstrate
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Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS. Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682

Related Resource References

Resource NameReference
Pharos CHEMBL1789941
PubChem 25126798
ChEMBL CHEMBL1789941
ChEBI CHEBI:66919