Duvelisib (IPI-145)
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MedKoo CAT#: 205744

CAS#: 1201438-56-3 (free)

Description: Duvelisib, also known as IPI-145 and INK-1197, is an orally bioavailable, highly selective and potent small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Upon administration, PI3K delta/gamma inhibitor IPI 145 prevents the activation of the PI3K delta/gamma-mediated signaling pathways which may lead to a reduction in cellular proliferation in PI3K delta/gamma-expressing tumor cells. Unlike other isoforms of PI3K, the delta and gamma isoforms are overexpressed primarily in hematologic malignancies and inflammatory and autoimmune diseases.


Chemical Structure

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Duvelisib (IPI-145)
CAS# 1201438-56-3 (free)

Theoretical Analysis

MedKoo Cat#: 205744
Name: Duvelisib (IPI-145)
CAS#: 1201438-56-3 (free)
Chemical Formula: C22H17ClN6O
Exact Mass: 416.11524
Molecular Weight: 416.86
Elemental Analysis: C, 63.39; H, 4.11; Cl, 8.50; N, 20.16; O, 3.84

Price and Availability

Size Price Availability Quantity
25.0mg USD 120.0 Same day
50.0mg USD 190.0 Same day
100.0mg USD 350.0 Same day
200.0mg USD 650.0 Same day
500.0mg USD 1250.0 Same day
1.0g USD 2150.0 2 weeks
2.0g USD 3350.0 2 weeks
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Related CAS #: 1386861-49-9 (hydrate)   1201438-56-3 (free)    

Synonym: IPI145; IPI 145; IPI-145. INK1197; INK 1197; INK-1197; Duvelisib; Copiktra。

IUPAC/Chemical Name: (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one

InChi Key: SJVQHLPISAIATJ-ZDUSSCGKSA-N

InChi Code: InChI=1S/C22H17ClN6O/c1-13(28-21-19-20(25-11-24-19)26-12-27-21)17-10-14-6-5-9-16(23)18(14)22(30)29(17)15-7-3-2-4-8-15/h2-13H,1H3,(H2,24,25,26,27,28)/t13-/m0/s1

SMILES Code: O=C1N(C2=CC=CC=C2)C([C@@H](NC3=C4N=CNC4=NC=N3)C)=CC5=C1C(Cl)=CC=C5

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 416.86 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548824/ PubMed PMID: 31644131.

2: Patel K, Danilov AV, Pagel JM. Duvelisib for CLL/SLL and follicular non-Hodgkin lymphoma. Blood. 2019 Nov 7;134(19):1573-1577. doi: 10.1182/blood.2019001795. PubMed PMID: 31554637.

3: Flinn IW, Cherry MA, Maris MB, Matous JV, Berdeja JG, Patel M. Combination trial of duvelisib (IPI-145) with rituximab or bendamustine/rituximab in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia. Am J Hematol. 2019 Dec;94(12):1325-1334. doi: 10.1002/ajh.25634. Epub 2019 Oct 4. PubMed PMID: 31490009.

4: Frustaci AM, Tedeschi A, Deodato M, Zamprogna G, Cairoli R, Montillo M. Duvelisib: a new phosphoinositide-3-kinase inhibitor in chronic lymphocytic leukemia. Future Oncol. 2019 Jul;15(19):2227-2239. doi: 10.2217/fon-2018-0881. Epub 2019 May 29. PubMed PMID: 31137964.

5: Rodrigues DA, Sagrillo FS, Fraga CAM. Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases. Pharmaceuticals (Basel). 2019 May 6;12(2). pii: E69. doi: 10.3390/ph12020069. PubMed PMID: 31064155; PubMed Central PMCID: PMC6631818.

6: Das M. Duvelisib in indolent non-Hodgkin lymphoma. Lancet Oncol. 2019 Mar;20(3):e138. doi: 10.1016/S1470-2045(19)30101-9. Epub 2019 Feb 21. PubMed PMID: 30799261.

7: Flinn IW, Miller CB, Ardeshna KM, Tetreault S, Assouline SE, Mayer J, Merli M, Lunin SD, Pettitt AR, Nagy Z, Tournilhac O, Abou-Nassar KE, Crump M, Jacobsen ED, de Vos S, Kelly VM, Shi W, Steelman L, Le N, Weaver DT, Lustgarten S, Wagner-Johnston ND, Zinzani PL. DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma. J Clin Oncol. 2019 Apr 10;37(11):912-922. doi: 10.1200/JCO.18.00915. Epub 2019 Feb 11. Erratum in: J Clin Oncol. 2019 Jun 1;37(16):1448. PubMed PMID: 30742566.

8: Brown JR. DUO delivers for duvelisib. Blood. 2018 Dec 6;132(23):2422-2424. doi: 10.1182/blood-2018-10-879650. PubMed PMID: 30523122; PubMed Central PMCID: PMC6284219.

9: Blair HA. Duvelisib: First Global Approval. Drugs. 2018 Nov;78(17):1847-1853. doi: 10.1007/s40265-018-1013-4. Review. PubMed PMID: 30430368.

10: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK532492/ PubMed PMID: 30371996.

11: Duvelisib Approved for Leukemia, Lymphoma. Cancer Discov. 2018 Dec;8(12):OF4. doi: 10.1158/2159-8290.CD-NB2018-137. Epub 2018 Oct 23. PubMed PMID: 30352859.

12: Das M. Duvelisib in haematological malignancies. Lancet Oncol. 2018 Nov;19(11):e586. doi: 10.1016/S1470-2045(18)30756-3. Epub 2018 Oct 11. PubMed PMID: 30318318.

13: Flinn IW, Hillmen P, Montillo M, Nagy Z, Illés Á, Etienne G, Delgado J, Kuss BJ, Tam CS, Gasztonyi Z, Offner F, Lunin S, Bosch F, Davids MS, Lamanna N, Jaeger U, Ghia P, Cymbalista F, Portell CA, Skarbnik AP, Cashen AF, Weaver DT, Kelly VM, Turnbull B, Stilgenbauer S. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood. 2018 Dec 6;132(23):2446-2455. doi: 10.1182/blood-2018-05-850461. Epub 2018 Oct 4. PubMed PMID: 30287523; PubMed Central PMCID: PMC6284216.

14: O'Brien S, Patel M, Kahl BS, Horwitz SM, Foss FM, Porcu P, Jones J, Burger J, Jain N, Allen K, Faia K, Douglas M, Stern HM, Sweeney J, Kelly P, Kelly V, Flinn I. Duvelisib, an oral dual PI3K-δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study. Am J Hematol. 2018 Nov;93(11):1318-1326. doi: 10.1002/ajh.25243. Epub 2018 Oct 20. PubMed PMID: 30094870.

15: Faia K, White K, Murphy E, Proctor J, Pink M, Kosmider N, McGovern K, Kutok J. The phosphoinositide-3 kinase (PI3K)-δ,γ inhibitor, duvelisib shows preclinical synergy with multiple targeted therapies in hematologic malignancies. PLoS One. 2018 Aug 1;13(8):e0200725. doi: 10.1371/journal.pone.0200725. eCollection 2018. PubMed PMID: 30067771; PubMed Central PMCID: PMC6070190.

16: Flinn IW, Patel M, Oki Y, Horwitz S, Foss FF, Allen K, Douglas M, Stern H, Sweeney J, Kharidia J, Kelly P, Kelly VM, Kahl B. Duvelisib, an oral dual PI3K-δ, γ inhibitor, shows clinical activity in indolent non-Hodgkin lymphoma in a phase 1 study. Am J Hematol. 2018 Nov;93(11):1311-1317. doi: 10.1002/ajh.25228. Epub 2018 Aug 31. PubMed PMID: 30033575; PubMed Central PMCID: PMC6220789.

17: Kawada JI, Ando S, Torii Y, Watanabe T, Sato Y, Ito Y, Kimura H. Antitumor effects of duvelisib on Epstein-Barr virus-associated lymphoma cells. Cancer Med. 2018 Apr;7(4):1275-1284. doi: 10.1002/cam4.1311. Epub 2018 Mar 9. PubMed PMID: 29522278; PubMed Central PMCID: PMC5911584.

18: Horwitz SM, Koch R, Porcu P, Oki Y, Moskowitz A, Perez M, Myskowski P, Officer A, Jaffe JD, Morrow SN, Allen K, Douglas M, Stern H, Sweeney J, Kelly P, Kelly V, Aster JC, Weaver D, Foss FM, Weinstock DM. Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. Blood. 2018 Feb 22;131(8):888-898. doi: 10.1182/blood-2017-08-802470. Epub 2017 Dec 12. PubMed PMID: 29233821; PubMed Central PMCID: PMC5824337.

19: Flinn IW, O'Brien S, Kahl B, Patel M, Oki Y, Foss FF, Porcu P, Jones J, Burger JA, Jain N, Kelly VM, Allen K, Douglas M, Sweeney J, Kelly P, Horwitz S. Duvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies. Blood. 2018 Feb 22;131(8):877-887. doi: 10.1182/blood-2017-05-786566. Epub 2017 Nov 30. PubMed PMID: 29191916; PubMed Central PMCID: PMC6033052.

20: Vangapandu HV, Jain N, Gandhi V. Duvelisib: a phosphoinositide-3 kinase δ/γ inhibitor for chronic lymphocytic leukemia. Expert Opin Investig Drugs. 2017 May;26(5):625-632. doi: 10.1080/13543784.2017.1312338. Epub 2017 Apr 13. Review. PubMed PMID: 28388280; PubMed Central PMCID: PMC5584596.



Additional Information

   
History: In July 2010, Intellikine announced a collaborative partnership with Infinity Pharmaceuticals, Inc. under which Infinity obtained global development and commercialization rights to IntellikineÂ’s portfolio of inhibitors of the delta and gamma isoforms of phosphoinositide-3-kinase (PI3K). Among these inhibitors is IPI-145, an orally available PI3Kδ/γ inhibitor which entered clinical study in October 2011.  The first Phase 1 trial of IPI-145 is a double-blind, randomized, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple escalating doses of IPI-145 in healthy adult subjects.  The second Phase 1 trial is an open-label, dose-escalation study designed to evaluate the safety, pharmacokinetics and clinical activity of IPI-145 in patients with advanced hematologic malignancies. Following the determination of the maximum tolerated dose in the dose escalation phase, an expansion phase will follow in patients with selected hematologic malignancies. (source: http://www.intellikine.com/pipeline/ipi145.html).