Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C28H32N4O3 |
| Molecular Weight | 472.5797 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 2 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C(CN1CCCC1)OC2=CC=C3C=C2COC\C=C\COCC4=CC(=CC=C4)C5=CC=NC(N5)=N3
InChI
InChIKey=HWXVIOGONBBTBY-ONEGZZNKSA-N
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+
| Molecular Formula | C28H32N4O3 |
| Molecular Weight | 472.5797 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 2 |
| Optical Activity | NONE |
DescriptionSources: http://www.ctibiopharma.com/pipeline/pacritinib/Curator's Comment: Description was created based on several sources, including http://www.pmlive.com/pharma_news/baxter_licenses_cancer_drug_from_cti_in_$172m_deal_519143
https://www.drugs.com/history/pacritinib.html
Sources: http://www.ctibiopharma.com/pipeline/pacritinib/
Curator's Comment: Description was created based on several sources, including http://www.pmlive.com/pharma_news/baxter_licenses_cancer_drug_from_cti_in_$172m_deal_519143
https://www.drugs.com/history/pacritinib.html
Pacritinib (SB1518), discovered in Singapore at the labs of S*BIO Pte Ltd., is an oral tyrosine kinase inhibitor (TKI) with activity against two important activating mutations: Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development as well as inflammatory cytokine expression and immune responses. Activating mutations of JAK2 are implicated in certain blood-related cancers, including myeloproliferative neoplasms (MPNs), leukemia and certain solid tumors. FLT3 is a gene commonly found mutated in patients with acute myeloid leukemia (AML). Pacritinib has demonstrated encouraging results in Phase 1 and 2 studies for patients with myelofibrosis and may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anemia than has been seen in currently approved and in-development JAK inhibitors. Pacritinib is acquired by Cell Therapeutics, Inc. (CTI) and Baxter international and could effectively address an unmet medical need for patients living with myelofibrosis who face treatment-emergent thrombocytopenia on marketed JAK inhibitors. Currently Pacritinib is undergoing preregistration for myelofibrosis.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21691275 |
23.0 nM [IC50] | ||
Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21691275 |
22.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25600203 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
PACRITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
9.2 μg/mL |
600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PACRITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
29 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25600203 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
PACRITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
161.3 μg × h/mL |
600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PACRITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
25 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25600203 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
PACRITINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no [IC50 >5 uM] | ||||
| no [IC50 >5 uM] | ||||
| no [IC50 >5 uM] | ||||
| no [IC50 >5 uM] | ||||
| no [IC50 >5 uM] | ||||
| yes [IC50 4.6109 uM] | ||||
| yes [Inhibition 10 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25600203/ |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25600203/ |
yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | ||||
| no | ||||
| no |
PubMed
| Title | Date | PubMed |
|---|---|---|
| SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. | 2011-11 |
|
| 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. | 2011-07-14 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02055781
Pacritinib 400 mg taken orally, once daily
Pacritinib 200 mg taken orally, twice daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22829080
Pacritinib inhibits cell proliferation of FLT3-ITD-harboring cells MV4-11 and primary AML blast cells with IC50s of 47 nM and 0.19-1.3 uM, respectively.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Apr 02 15:35:08 GMT 2025
by
admin
on
Wed Apr 02 15:35:08 GMT 2025
|
| Record UNII |
G22N65IL3O
|
| Record Status |
FAILED
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Official Name | English | ||
|
Preferred Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English |
| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
|
EU-Orphan Drug |
EU/3/10/767
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
||
|
FDA ORPHAN DRUG |
245607
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
||
|
NCI_THESAURUS |
C125450
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
||
|
NCI_THESAURUS |
C129825
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
BC-48
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
DB11697
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
46216796
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
SUB114513
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
G22N65IL3O
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
2595243
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
DTXSID801045679
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
937272-79-2
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
G22N65IL3O
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
C78837
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
9385
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
100000142107
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | |||
|
EU/3/10/767(POSITIVE)
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY | On 25 August 2010, orphan designation (EU/3/10/767) was granted by the European Commission to Voisin Consulting S.A.R.L., France, for 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 for the treatment of post-essential thrombocythaemia myelofibrosis. The sponsorship was transferred to Baxter Innovations GmbH, Austria, in March 2015. In May 2015, Baxter Innovations GmbH changed name to Baxalta Innovations GmbH. The sponsorship was transferred to CTI Life Sciences Ltd, United Kingdom, in November 2016. | ||
|
Pacritinib
Created by
admin on Wed Apr 02 15:35:08 GMT 2025 , Edited by admin on Wed Apr 02 15:35:08 GMT 2025
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
TARGET -> INHIBITOR |
IC50
|
||
|
SALT/SOLVATE -> PARENT |
|
||
|
TRANSPORTER -> INHIBITOR |
IC50
|
||
|
TRANSPORTER -> INHIBITOR |
IC50
|
||
|
TARGET -> INHIBITOR |
IC50
|
||
|
TRANSPORTER -> INHIBITOR |
IC50
|
||
|
TARGET -> INHIBITOR |
IC50
|
||
|
TARGET -> INHIBITOR |
IC50
|
||
|
SALT/SOLVATE -> PARENT |
|
||
|
TARGET -> INHIBITOR |
|
||
|
OFF-TARGET->INHIBITOR |
IC50
|
||
|
TARGET -> INHIBITOR |
IC50
|
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
METABOLITE LESS ACTIVE -> PARENT |
Predominant Metabolite in human studies
MAJOR
FECAL; PLASMA; URINE
|
||
|
METABOLITE -> PARENT |
MINOR
PLASMA; URINE
|
||
|
METABOLITE INACTIVE -> PARENT |
MINOR
FECAL
|
||
|
|
METABOLITE -> PARENT |
FECAL; PLASMA; URINE
|
||
|
METABOLITE INACTIVE -> PARENT |
MINOR
FECAL
|
||
|
METABOLITE INACTIVE -> PARENT |
MINOR
FECAL
|
||
|
METABOLITE -> PARENT |
PLASMA; URINE
|
||
|
METABOLITE LESS ACTIVE -> PARENT |
Major metabolite in animal species lesser metabolite in human studies. Has 50% of the activity of the parent
MAJOR
PLASMA
|
||
|
METABOLITE INACTIVE -> PARENT |
MINOR
FECAL
|
||
|
METABOLITE -> PARENT |
FECAL; PLASMA; URINE
|
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
ACTIVE MOIETY |
|