pacritinib

ID: ALA2035187

Chembl Id: CHEMBL2035187

Max Phase: Approved

First Approval: 2022

Molecular Formula: C28H32N4O3

Molecular Weight: 472.59

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Pacritinib | Sb-1518 | ONX-0803 | SB-1518 | SB1518

Synonyms from Alternative Forms(1): Vonjo

Canonical SMILES:  C1=N/C2=N/c3ccc(OCCN4CCCC4)c(c3)COC/C=C/COCc3cccc(c3)C(=C1)N2

Standard InChI:  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+

Standard InChI Key:  HWXVIOGONBBTBY-ONEGZZNKSA-N

Alternative Forms

1. Parent:

   

   ALA2035187

   PACRITINIB

2. Alternative Forms:

   

   ALA2035187

   Pacritinib citrate

Molecule Features

Natural Product: No

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: Yes

Prodrug: No

Calculated Properties

Molecular Weight: 472.59

Molecular Weight (Monoisotopic): 472.2474

AlogP: 4.47

#Rotatable Bonds: 4

Polar Surface Area: 67.68

Molecular Species: BASE

HBA: 7

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 8.68

CX LogP: 3.26

CX LogD: 1.96

Aromatic Rings: 2

Heavy Atoms: 35

QED Weighted: 0.67

Np Likeness Score: 0.11

References

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2. William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Tan E, Chen D, Williams M, Sun ET, Goh KC, Ong WC, Goh SK, Hart S, Jayaraman R, Pasha MK, Ethirajulu K, Wood JM, Dymock BW..  (2011)  Discovery of the macrocycle 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 (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma.,  54  (13): [PMID:21604762] [10.1021/jm200326p]

3. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

4. Unpublished dataset, 

5. Yang EG, Mustafa N, Tan EC, Poulsen A, Ramanujulu PM, Chng WJ, Yen JJ, Dymock BW..  (2016)  Design and Synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) Bispecific Inhibitors Based on Pacritinib and Evidence of Dual Pathway Inhibition in Hematological Cell Lines.,  59  (18): [PMID:27541357] [10.1021/acs.jmedchem.6b00157]

6. Klaeger S, Heinzlmeir S and Wilhelm M et al.  (2017)  The target landscape of clinical kinase drugs.,  358  (6367): [PMID:29191878] [10.1126/science.aan4368]

7. Yao L, Mustafa N, Tan EC, Poulsen A, Singh P, Duong-Thi MD, Lee JXT, Ramanujulu PM, Chng WJ, Yen JJY, Ohlson S, Dymock BW..  (2017)  Design and Synthesis of Ligand Efficient Dual Inhibitors of Janus Kinase (JAK) and Histone Deacetylase (HDAC) Based on Ruxolitinib and Vorinostat.,  60  (20): [PMID:28953386] [10.1021/acs.jmedchem.7b00678]

8. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

9. Katie Heiser, Peter F. McLean, Chadwick T. Davis, Ben Fogelson, Hannah B. Gordon, Pamela Jacobson, Brett Hurst, Ben Miller, Ronald W. Alfa, Berton A. Earnshaw, Mason L. Victors, Yolanda T. Chong, Imran S. Haque, Adeline S. Low, Christopher C. Gibson.  (2020)  Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2,  [10.1101/2020.04.21.054387]

10. Yang T, Hu M, Qi W, Yang Z, Tang M, He J, Chen Y, Bai P, Yuan X, Zhang C, Liu K, Lu Y, Xiang M, Chen L..  (2019)  Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms.,  62  (22): [PMID:31670517] [10.1021/acs.jmedchem.9b01348]

11. Yuan T, Qi B, Jiang Z, Dong W, Zhong L, Bai L, Tong R, Yu J, Shi J..  (2019)  Dual FLT3 inhibitors: Against the drug resistance of acute myeloid leukemia in recent decade.,  178  [PMID:31207462] [10.1016/j.ejmech.2019.06.002]

12. Li Y, Ye T, Xu L, Dong Y, Luo Y, Wang C, Han Y, Chen K, Qin M, Liu Y, Zhao Y..  (2019)  Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3.,  181  [PMID:31408808] [10.1016/j.ejmech.2019.111590]

13. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

14. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

15. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

16. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

17. WHO Anatomical Therapeutic Chemical Classification, 

18. Raghuvanshi R, Bharate SB..  (2022)  Recent Developments in the Use of Kinase Inhibitors for Management of Viral Infections.,  65  (2.0): [PMID:33539089] [10.1021/acs.jmedchem.0c01467]

19. Wang Z, Cai J, Cheng J, Yang W, Zhu Y, Li H, Lu T, Chen Y, Lu S..  (2021)  FLT3 Inhibitors in Acute Myeloid Leukemia: Challenges and Recent Developments in Overcoming Resistance.,  64  (6.0): [PMID:33719439] [10.1021/acs.jmedchem.0c01851]

20. Acharya B, Saha D, Armstrong D, Lakkaniga NR, Frett B..  (2022)  FLT3 inhibitors for acute myeloid leukemia: successes, defeats, and emerging paradigms.,  13  (7.0): [PMID:35923716] [10.1039/d2md00067a]

Source

Source(8):

• Scientific Literature
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names
• WHO Anatomical Therapeutic Chemical Classification
• Kuster lab chemical proteomics drug profiling
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6