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MedKoo Cat#: 205744 | Name: Duvelisib (IPI-145)
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Duvelisib (IPI-145)
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: 416.1152

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
25mg USD 120.00 Ready to ship
50mg USD 190.00 Ready to ship
100mg USD 350.00 Ready to ship
200mg USD 600.00 Ready to ship
500mg USD 1,250.00 Ready to ship
1g USD 2,150.00 2 weeks
2g USD 3,350.00 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
More Info
    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).      
Biological target:
Duvelisib (IPI-145) is a p100δ inhibitor with IC50 of 2.5 nM, 27.4 nM, 85 nM and 1602 nM for p110δ, P110γ, p110β and p110α, respectively.
In vitro activity:
Duvelisib inhibited cell growth in EBV‐positive and ‐negative B cell lines, except in P3HR1, in a dose‐dependent manner (Fig. 1A and B). Cell growth inhibition of EBV‐negative T cell lines Jurkat, MOLT4, and EBV‐positive NK cell line KAI3, was also observed at 1 or 5 μmol/L of duvelisib. However, no growth inhibition was observed in EBV‐positive SNT16 and EBV‐negative KHYG1. Overall, B cell lines were more susceptible to duvelisib than T and NK cell lines, and further experiments with duvelisib were focused on EBV‐positive and ‐negative B cell lines. Reference: Cancer Med. 2018 Apr; 7(4): 1275–1284. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911584/
In vivo activity:
To examine the effect of duvelisib in vivo, this study injected mice with 0.5 × 106 U266-luc cells via the tail vein. Mice were treated daily for 10 days with duvelisib (15 mg/kg on days 5–14 following transplant). On day 18 after transplant (4 days after completion of the 10- day duvelisib treatment), duvelisib-treated animals had reduced tumour burden when compared to vehicle control treated animals, as measured by bioluminescence (Figure 6c). Furthermore, Kaplan–Meier analysis shows significant survival improvement in the duvelisib-treated group when compared to the control-treated group (Figure 6d). Reference: Blood Cancer J. 2017 Mar; 7(3): e539. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380901/
Solvent mg/mL mM
Solubility
DMSO 45.0 107.95
DMSO:PBS (pH 7.2) (1:1) 0.5 1.20
DMF 10.0 23.99
Ethanol 10.0 23.99
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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
Formulation protocol:
1. 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. PMID: 29522278; PMCID: PMC5911584. 2. Balakrishnan K, Peluso M, Fu M, Rosin NY, Burger JA, Wierda WG, Keating MJ, Faia K, O'Brien S, Kutok JL, Gandhi V. The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL. Leukemia. 2015 Sep;29(9):1811-22. doi: 10.1038/leu.2015.105. Epub 2015 Apr 28. PMID: 25917267; PMCID: PMC4558374. 3. Piddock RE, Loughran N, Marlein CR, Robinson SD, Edwards DR, Yu S, Pillinger GE, Zhou Z, Zaitseva L, Auger MJ, Rushworth SA, Bowles KM. PI3Kδ and PI3Kγ isoforms have distinct functions in regulating pro-tumoural signalling in the multiple myeloma microenvironment. Blood Cancer J. 2017 Mar 10;7(3):e539. doi: 10.1038/bcj.2017.16. PMID: 28282033; PMCID: PMC5380901. 4. Winkler DG, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, Pink MM, Proctor JL, Lussier J, Martin CM, Hoyt JG, Tillotson B, Murphy EL, Lim AR, Thomas BD, Macdougall JR, Ren P, Liu Y, Li LS, Jessen KA, Fritz CC, Dunbar JL, Porter JR, Rommel C, Palombella VJ, Changelian PS, Kutok JL. PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74. doi: 10.1016/j.chembiol.2013.09.017. Epub 2013 Nov 7. PMID: 24211136.
In vitro protocol:
1. 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. PMID: 29522278; PMCID: PMC5911584. 2. Balakrishnan K, Peluso M, Fu M, Rosin NY, Burger JA, Wierda WG, Keating MJ, Faia K, O'Brien S, Kutok JL, Gandhi V. The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL. Leukemia. 2015 Sep;29(9):1811-22. doi: 10.1038/leu.2015.105. Epub 2015 Apr 28. PMID: 25917267; PMCID: PMC4558374.
In vivo protocol:
1. Piddock RE, Loughran N, Marlein CR, Robinson SD, Edwards DR, Yu S, Pillinger GE, Zhou Z, Zaitseva L, Auger MJ, Rushworth SA, Bowles KM. PI3Kδ and PI3Kγ isoforms have distinct functions in regulating pro-tumoural signalling in the multiple myeloma microenvironment. Blood Cancer J. 2017 Mar 10;7(3):e539. doi: 10.1038/bcj.2017.16. PMID: 28282033; PMCID: PMC5380901. 2. Winkler DG, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, Pink MM, Proctor JL, Lussier J, Martin CM, Hoyt JG, Tillotson B, Murphy EL, Lim AR, Thomas BD, Macdougall JR, Ren P, Liu Y, Li LS, Jessen KA, Fritz CC, Dunbar JL, Porter JR, Rommel C, Palombella VJ, Changelian PS, Kutok JL. PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74. doi: 10.1016/j.chembiol.2013.09.017. Epub 2013 Nov 7. PMID: 24211136.
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.

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DT2216-isomer

DT2216-isomer

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