6T3

11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Created:	2016-06-17
Last modified:	2017-11-29

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2 entries where 6T3 is found as a standalone ligand

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Chemical Details
Formal Charge	0
Atom Count	67
Chiral Atom Count	0
Bond Count	71
Aromatic Bond Count	18

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Chemical Component Summary
Name	11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene
Formula	C₂₈ H₃₂ N₄ O₃
Molecular Weight	472.579
Type	NON-POLYMER

Chemical Descriptors
Type	Program	Version	Descriptor
SMILES	CACTVS	3.385	C1CCN(C1)CCOc2ccc3Nc4nccc(n4)c5cccc(COCC=CCOCc2c3)c5
SMILES	OpenEye OEToolkits	2.0.5	c1cc2cc(c1)-c3ccnc(n3)Nc4ccc(c(c4)COCC=CCOC2)OCCN5CCCC5
Canonical SMILES	CACTVS	3.385	C1CCN(C1)CCOc2ccc3Nc4nccc(n4)c5cccc(COC/C=C/COCc2c3)c5
Canonical SMILES	OpenEye OEToolkits	2.0.5	c1cc2cc(c1)-c3ccnc(n3)Nc4ccc(c(c4)COC/C=C/COC2)OCCN5CCCC5
InChI	InChI	1.03	InChI=1S/C28H32N4O3/c1-2-13-32(12-1)14-17-35-27-9-8-25-19-24(27)21-34-16-4-3-15-33-20-22-6-5-7-23(18-22)26-10-11-29-28(30-25)31-26/h3-11,18-19H,1-2,12-17,20-21H2,(H,29,30,31)/b4-3+
InChIKey	InChI	1.03	HWXVIOGONBBTBY-ONEGZZNKSA-N

Drug Info: DrugBank

DrugBank ID	DB11697
Name	Pacritinib
Groups	approved investigational
Description	Myelofibrosis (MF) is a rare disorder characterized by hematopoietic abnormalities and fibrosis within the bone marrow.[L40793] The underlying cause of primary MF is unknown, but secondary MF can arise in patients with a history of polycythemia vera or essential thrombocythemia.[L40793] While some patients may remain asymptomatic, typical symptoms of MF arise from abnormalities in blood cell production and may therefore include various cytopenias, infections, splenomegaly, and general systemic symptoms such as fever.[L40793] Approximately 50% of patients with primary MF have a mutation of the _JAK2_ gene, which is also commonly mutated in patients with polycythemia vera or essential thrombocythemia.[L40793] JAK2 signaling is important for hematopoiesis and proper immune functioning,[L40754] and while the precise role it plays in the pathogenesis of MF remains unclear, its clear association with MF has made it a desirable therapeutic target in MF treatment. Pacritinib is an inhibitor of both wild-type and mutant (V617F) JAK2, as well as FMS-like tyrosine kinase 3 (FLT3), which was granted accelerated approval by the FDA in February 2022 for the treatment of both primary and secondary MF in patients with platelet counts < 50 x 10<sup>9</sup>/L.[L40754] It provides a treatment option for patients who have MF with severe thrombocytopenia, which occurs in approximately one-third of MF patients and carries with it a particularly poor prognosis.[L40709]
Synonyms	Pacritinib Pacritinibum
Brand Names	Vonjo
Indication	Pacritinib is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 x 10<sup>9</sup>/L.[L40754] This indication is approved under accelerated approval based on spleen volume reduction. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.[L40754]
Categories	Antineoplastic Agents Antineoplastic and Immunomodulating Agents BCRP/ABCG2 Inhibitors Cytochrome P-450 CYP1A2 Inducers Cytochrome P-450 CYP1A2 Inducers (strength unknown) Cytochrome P-450 CYP1A2 Inhibitors Cytochrome P-450 CYP1A2 Inhibitors (strength unknown) Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2C19 inhibitors (strength unknown) Cytochrome P-450 CYP3A Inducers Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Inducers Cytochrome P-450 CYP3A4 Inducers (strength unknown) Cytochrome P-450 CYP3A4 Inhibitors Cytochrome P-450 CYP3A4 Inhibitors (strength unknown) Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 Enzyme Inducers Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Substrates Janus Kinase 2, antagonists & inhibitors Janus Kinase Inhibitor Janus Kinases, antagonists & inhibitors Kinase Inhibitor OCT1 inhibitors OCT2 Inhibitors P-glycoprotein inhibitors Potential QTc-Prolonging Agents Protein Kinase Inhibitors QTc Prolonging Agents Tyrosine Kinase Inhibitors
ATC-Code	L01EJ03
CAS number	937272-79-2

Drug Targets

Name	Target Sequence	Pharmacological Action	Actions
Tyrosine-protein kinase JAK2	MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKS...	unknown	inhibitor
Receptor-type tyrosine-protein kinase FLT3	MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKS...	unknown	inhibitor
Cytochrome P450 3A4	MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNI...	unknown	substrate,inhibitor,inducer
Cytochrome P450 1A2	MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPL...	unknown	inhibitor,inducer
Cytochrome P450 2C19	MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDV...	unknown	inhibitor
P-glycoprotein 1	MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLY...	unknown	inhibitor
ATP-binding cassette sub-family G member 2	MSSSNVEVFIPVSQGNTNGFPATASNDLKAFTEGAVLSFHNICYRVKLKS...	unknown	inhibitor
Solute carrier family 22 member 1	MPTVDDILEQVGESGWFQKQAFLILCLLSAAFAPICVGIVFLGFTPDHHC...	unknown	inhibitor
Solute carrier family 22 member 2	MPTTVDDVLEHGGEFHFFQKQMFFLLALLSATFAPIYVGIVFLGFTPDHR...	unknown	inhibitor
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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