U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C19H23N9O
Molecular Weight 393.4456
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PRT-062607

SMILES

N[C@H]1CCCC[C@H]1NC2=NC=C(C(N)=O)C(NC3=CC=CC(=C3)N4N=CC=N4)=N2

InChI

InChIKey=TXGKRVFSSHPBAJ-JKSUJKDBSA-N
InChI=1S/C19H23N9O/c20-15-6-1-2-7-16(15)26-19-22-11-14(17(21)29)18(27-19)25-12-4-3-5-13(10-12)28-23-8-9-24-28/h3-5,8-11,15-16H,1-2,6-7,20H2,(H2,21,29)(H2,22,25,26,27)/t15-,16+/m0/s1

HIDE SMILES / InChI
Molecular Formula C19H23N9O
Molecular Weight 393.4456
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22040680 | https://www.ncbi.nlm.nih.gov/pubmed/27406873

PRT062607 (BIIB-057; P 50515 PRT-2607; PRT062607) is a highly specific and potent inhibitor of spleen tyrosine kinase (Syk). PRT062607 (BIIB-057) has a desirable pharmacokinetics profile and is capable of safely, potently, and selectively suppressing SYK kinase function in humans following once-daily oral dosing. The compound is being evaluated for the treatment of chronic inflammatory diseases; including rheumatoid arthritis, systemic lupus erythematosus, non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Phase I development is underway in the US and the UK for the treatment of patients with inflammation and cancer. Phase I development is also being conducted in rheumatoid arthritis and systemic lupus erythematosus, presumably in the US.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 1.0 nM [IC50]
Inhibitor
8297
 81.0 nM [IC50]
Inhibitor
8297
 88.0 nM [IC50]
Inhibitor
8297
 123.0 nM [IC50]
Inhibitor
8297
 139.0 nM [IC50]
Inhibitor
8297
 1.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
557 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27406873
110 mg 1 times / day steady-state, oral
dose: 110 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PRT062607 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
996 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27406873
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PRT062607 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
8487 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27406873
110 mg 1 times / day steady-state, oral
dose: 110 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PRT062607 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
22300 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27406873
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PRT062607 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
75.3 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27406873
110 mg 1 times / day steady-state, oral
dose: 110 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PRT062607 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
65.1 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/27406873
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PRT062607 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
400 mg single, oral
Highest studied dose
Dose: 400 mg
Route: oral
Route: single
Dose: 400 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/27406873
Page: p.203
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/27406873
Page: p.203
Sources:
https://pubmed.ncbi.nlm.nih.gov/27406873
Page: p.203
110 mg 1 times / day steady-state, oral
Studied dose
Dose: 110 mg, 1 times / day
Route: oral
Route: steady-state
Dose: 110 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/27406873
Page: p.204
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: unknown
Food Status: UNKNOWN
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/27406873
Page: p.204
Sources:
https://pubmed.ncbi.nlm.nih.gov/27406873
Page: p.204
PubMed

PubMed

TitleDatePubMed
Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis.
2012 Feb
Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migration.
2012 Jul
Methotrexate and a spleen tyrosine kinase inhibitor cooperate to inhibit responses to peripheral blood B cells in rheumatoid arthritis.
2013 Dec
The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia.
2013 Feb
Selective spleen tyrosine kinase inhibition delays autoimmune arthritis in mice.
2015 Aug
PRT062607 Achieves Complete Inhibition of the Spleen Tyrosine Kinase at Tolerated Exposures Following Oral Dosing in Healthy Volunteers.
2017 Feb
Patents

Patents

20100048567
2
20120101275
2
20120130073
2
20130165431
2

Sample Use Guides

In Vivo Use Guide
Curator's Comment: PRT062607 (BIIB-057) has a desirable pharmacokinetics profile and is capable of safely, potently, and selectively suppressing SYK kinase function in humans following once-daily oral dosing.
Unknown
Route of Administration: Oral
In Vitro Use Guide
BIIB-057 (P505-15) potently inhibited B cell antigen receptor-mediated B cell signaling and activation (IC50 0.27 and 0.28 uM, respectively) and Fcε receptor 1-mediated basophil degranulation (IC50 0.15 uM). Similar levels of ex vivo inhibition were measured after dosing in mice (Syk signaling IC50 0.32 uM).
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:29:26 UTC 2023
Edited
by admin
on Fri Dec 15 18:29:26 UTC 2023
Record UNII
K9C42672RH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PRT-062607
Code English
5-PYRIMIDINECARBOXAMIDE, 2-(((1R,2S)-2-AMINOCYCLOHEXYL)AMINO)-4-((3-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)AMINO)-
Systematic Name English
Code System Code Type Description
CAS
1370261-96-3
Created by admin on Fri Dec 15 18:29:26 UTC 2023 , Edited by admin on Fri Dec 15 18:29:26 UTC 2023
PRIMARY
FDA UNII
K9C42672RH
Created by admin on Fri Dec 15 18:29:26 UTC 2023 , Edited by admin on Fri Dec 15 18:29:26 UTC 2023
PRIMARY
PUBCHEM
44462758
Created by admin on Fri Dec 15 18:29:26 UTC 2023 , Edited by admin on Fri Dec 15 18:29:26 UTC 2023
PRIMARY
Related Record Type Details
Structure of PRT-062607 ACETATE
SALT/SOLVATE -> PARENT
TYROSINE-PROTEIN KINASE SYK
TARGET -> INHIBITOR
Related Record Type Details
Structure of PRT-062607
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966