Please Wait
Applying Filters...
menu
    • menu
    Granules India Limited has high volume world-class facilities for APIs, PFIs, & FDFs, serving customers in over 80 countries.

    Virtual Booth

    Contact Supplier

    Jai Radhe Sales is your partner for all your sourcing needs.

    Virtual Booth

    Contact Supplier

    xyz-pharma-m-2024-10-07

    Virtual Booth

    Contact Supplier

    Egis is a Hungarian generic pharma company with 110 years history. Our activities incorporate all areas of the pharma value chain.

    Virtual Booth

    Contact Supplier

    Biophore is a research-driven global pharmaceutical company focused on niche APIs for the generic industry.

    Virtual Booth

    Contact Supplier

    xyz-pharma-m-2024-10-07

    Virtual Booth

    Contact Supplier

    Menu

    Umbralisib

    DEVELOPMENTS

    INTERMEDIATES

    FINISHED DOSAGE FORMULATIONS

    DIGITAL CONTENT

    GLOBAL SALES INFORMATION

    PATENTS & EXCLUSIVITIES

    PharmaCompass
    Xls

    Filters

    clear-filterReset all filters
    2D Structure
    Also known as: 1532533-67-7, Tgr-1202, Rp-5264, Tgr1202, Rp5264, Tgr-1202 free base
    Molecular Formula
    C31H24F3N5O3
    Molecular Weight
    571.5  g/mol
    InChI Key
    IUVCFHHAEHNCFT-INIZCTEOSA-N
    FDA UNII
    38073MQB2A
    Umbralisib is an orally bioavailable, selective inhibitor of the delta isoform of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinases (PI3K) with potential antineoplastic activity. PI3K-delta inhibitor TGR-1202 inhibits PI3K and prevents the activation of the PI3K/AKT kinase signaling pathway. This decreases proliferation and induces cell death in susceptible tumor cells. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in tumor cells and cells of the hematopoietic lineage. The targeted inhibition of PI3K-delta allows for PI3K signaling in normal, non-neoplastic cells. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival.
    Umbralisib is a Kinase Inhibitor. The mechanism of action of umbralisib is as a Kinase Inhibitor.
    1 2D Structure

    2D Structure

    2 Identification
    2.1 Computed Descriptors
    2.1.1 IUPAC Name
    2-[(1S)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one
    2.1.2 InChI
    InChI=1S/C31H24F3N5O3/c1-15(2)41-24-9-7-18(12-22(24)34)27-26-30(35)36-14-37-31(26)39(38-27)16(3)29-25(17-5-4-6-19(32)11-17)28(40)21-13-20(33)8-10-23(21)42-29/h4-16H,1-3H3,(H2,35,36,37)/t16-/m0/s1
    2.1.3 InChI Key
    IUVCFHHAEHNCFT-INIZCTEOSA-N
    2.1.4 Canonical SMILES
    CC(C)OC1=C(C=C(C=C1)C2=NN(C3=NC=NC(=C23)N)C(C)C4=C(C(=O)C5=C(O4)C=CC(=C5)F)C6=CC(=CC=C6)F)F
    2.1.5 Isomeric SMILES
    C[C@@H](C1=C(C(=O)C2=C(O1)C=CC(=C2)F)C3=CC(=CC=C3)F)N4C5=NC=NC(=C5C(=N4)C6=CC(=C(C=C6)OC(C)C)F)N
    2.2 Other Identifiers
    2.2.1 UNII
    38073MQB2A
    2.3 Synonyms
    2.3.1 MeSH Synonyms

    1. Tgr-1202

    2. Ukoniq

    2.3.2 Depositor-Supplied Synonyms

    1. 1532533-67-7

    2. Tgr-1202

    3. Rp-5264

    4. Tgr1202

    5. Rp5264

    6. Tgr-1202 Free Base

    7. Ukoniq

    8. Umbralisib [usan]

    9. (s)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1h-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4h-chromen-4-one

    10. Tgr 1202

    11. Tgr-1202 Base

    12. 38073mqb2a

    13. 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one

    14. 2-((1s)-1-(4-amino-3-(3-fluoro-4-(1-methylethoxy)phenyl)-1h-pyrazolo(3,4-d)pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4h-1-benzopyran-4-one

    15. Umbralisib [inn]

    16. Umbralisib (usan/inn)

    17. Umbralisib [who-dd]

    18. Unii-38073mqb2a

    19. Gtpl8916

    20. Chembl3948730

    21. Schembl15557416

    22. Tgr 1202 [who-dd]

    23. Bdbm184556

    24. Dtxsid601337137

    25. Bcp24686

    26. Ex-a1645

    27. Mfcd28386165

    28. Nsc793696

    29. Nsc800405

    30. S8194

    31. Example A1 [us2014011819]

    32. Zinc141831516

    33. Ccg-270101

    34. Cs-5243

    35. Db14989

    36. Nsc-793696

    37. Nsc-800405

    38. Rp 5264

    39. Ac-33183

    40. As-52257

    41. Hy-12279

    42. Us9150579, B1

    43. D11322

    44. P14656

    45. A901657

    46. Q27088612

    47. (s)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1h-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4h-chromen-4-one;rp-5264

    48. 4h-1-benzopyran-4-one, 2-((1s)-1-(4-amino-3-(3-fluoro-4-(1-methylethoxy)phenyl)-1h-pyrazolo(3,4-d)pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-

    2.4 Create Date
    2014-03-03
    3 Chemical and Physical Properties
    Molecular Weight 571.5 g/mol
    Molecular Formula C31H24F3N5O3
    XLogP35.8
    Hydrogen Bond Donor Count1
    Hydrogen Bond Acceptor Count10
    Rotatable Bond Count6
    Exact Mass571.18312413 g/mol
    Monoisotopic Mass571.18312413 g/mol
    Topological Polar Surface Area105 Ų
    Heavy Atom Count42
    Formal Charge0
    Complexity1020
    Isotope Atom Count0
    Defined Atom Stereocenter Count1
    Undefined Atom Stereocenter Count0
    Defined Bond Stereocenter Count0
    Undefined Bond Stereocenter Count0
    Covalently Bonded Unit Count1
    4 Drug and Medication Information
    4.1 Drug Indication

    Umbralisib is indicated to treat relapsed or refractory marginal zone lymphoma (MZL) in patients who have received at least one prior anti-CD20-based regimen. It is also indicated for the treatment of relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

    5 Pharmacology and Biochemistry
    5.1 Pharmacology

    Umbralisib acts against against marginal zone lymphoma by interrupting the PI3K pathway; this is an essential pathway for B-cell receptor signaling responsible for the progression of lymphoma. In addition, Umbralisib inhibits other pathways involved in specific types of lymphoma, including the casein kinase pathway. An overall response rate of 55% was recorded during clinical trials and the rate of 1-year progression free survival from marginal zone lymphoma was 71%. A relationship between higher umbralisib steady state exposures and higher incidence of adverse reactions, including diarrhea and elevated AST/ALT was observed during clinical studies. The effect of this drug on QT interval has not been fully characterized.

    5.2 FDA Pharmacological Classification
    5.2.1 Active Moiety
    UMBRALISIB
    5.2.2 FDA UNII
    38073MQB2A
    5.2.3 Pharmacological Classes
    Mechanisms of Action [MoA] - Kinase Inhibitors
    5.3 Absorption, Distribution and Excretion

    Absorption

    Umbralisib is rapidly absorbed in the GI tract. The Tmax of umbralisib is about 4 hours. After consumption of a high-fat, high calorie meal with umbralisib, the AUC increased by 61% and the Cmax increased by 115%.

    Route of Elimination

    During pharmacokinetic studies, about 81% of the umbralisib dose was recovered in feces (17% unchanged). Approximately 3% was detected in the urine (0.02% unchanged) after a radiolabeled dose of 800 mg in healthy volunteers.

    Volume of Distribution

    The average apparent central volume of distribution of umbralisib is 312 L.

    Clearance

    The average apparent clearance of umbralisib is 15.5 L/h.

    5.4 Metabolism/Metabolites

    During in vitro studies, umbralisib was metabolized by CYP2C9, CYP3A4, and CYP1A2 enzymes.

    5.5 Biological Half-Life

    The effective half-life of Umbralisib is about 91 hours.

    5.6 Mechanism of Action

    The PI3K pathway is a deregulated in malignancies, leading to the overexpression of p110 isoforms (p110, p110, p110, p110) that induces malignant transformation in cells. Umbralisib inhibits several protein kinases, including PI3K and casein kinase CK1. PI3K is expressed in both healthy cells and malignant B-cells. CK1 is believed to be involved in the pathogenesis of malignant cells, including lymphomas. This results in reduced progression of relapsed or refractory lymphoma. In biochemical assays, umbralisib inhibited a mutated form of ABL1. In vitro, umbralisib inhibits malignant cell proliferation, CXCL12-mediated cell adhesion, and CCL19-mediated cell migration.