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

Details

Stereochemistry ACHIRAL
Molecular Formula C25H26N8O
Molecular Weight 454.5279
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PIMITESPIB

SMILES

CCc1cc(ccc1-n2c3c(c(ccn3)-n4cc(-c5cnn(C)c5)nc4)c(C(C)C)n2)C(=O)N

InChI

InChIKey=NVVPMZUGELHVMH-UHFFFAOYSA-N
InChI=1S/C25H26N8O/c1-5-16-10-17(24(26)34)6-7-20(16)33-25-22(23(30-33)15(2)3)21(8-9-27-25)32-13-19(28-14-32)18-11-29-31(4)12-18/h6-15H,5H2,1-4H3,(H2,26,34)

HIDE SMILES / InChI

Molecular Formula C25H26N8O
Molecular Weight 454.5279
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/28062703

TAS-116 is a highly potent oral HSP90 inhibitor with unique tissue distribution properties. TAS-116 has the potential to demonstrate antitumor activity, while being designed to limit certain adverse events by unique tissue distribution. Phase-II clinical trials in gastrointestinal stromal tumours are ongoing in Japan.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
34.7 nM [Ki]
21.3 nM [Ki]
Conditions

Conditions

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2756 ng/mL
210.7 mg/m² 1 times / 2 days multiple, oral
dose: 210.7 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3080 ng/mL
107.5 mg/m² 1 times / day multiple, oral
dose: 107.5 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2587 ng/mL
107.5 mg/m² single, oral
dose: 107.5 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3097 ng/mL
210.7 mg/m² single, oral
dose: 210.7 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
33090 ng × h/mL
210.7 mg/m² 1 times / 2 days multiple, oral
dose: 210.7 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
38923 ng × h/mL
107.5 mg/m² 1 times / day multiple, oral
dose: 107.5 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
36779 ng × h/mL
107.5 mg/m² single, oral
dose: 107.5 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
47365 ng × h/mL
210.7 mg/m² single, oral
dose: 210.7 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9.91 h
210.7 mg/m² 1 times / 2 days multiple, oral
dose: 210.7 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
12.76 h
107.5 mg/m² 1 times / day multiple, oral
dose: 107.5 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
13.21 h
107.5 mg/m² single, oral
dose: 107.5 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
13.32 h
210.7 mg/m² single, oral
dose: 210.7 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
TAS-116 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
295 mg/m2 1 times / 2 days multiple, oral
Highest studied dose
Dose: 295 mg/m2, 1 times / 2 days
Route: oral
Route: multiple
Dose: 295 mg/m2, 1 times / 2 days
Sources: Page: p.533, 534, 536
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.533, 534, 536
DLT: Septic shock, Pneumonia...
Disc. AE: Anemia...
Dose limiting toxicities:
Septic shock (grade 4, 20%)
Pneumonia (grade 4, 20%)
Febrile neutropenia (grade 3, 20%)
Platelet count decreased (grade 3, 20%)
Respiratory failure (grade 4, 20%)
AEs leading to
discontinuation/dose reduction:
Anemia (grade 3, 20%)
Sources: Page: p.533, 534, 536
107.5 mg/m2 1 times / day multiple, oral
MTD
Dose: 107.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 107.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
DLT: Anorexia...
Disc. AE: Cystitis, Macular edema...
Dose limiting toxicities:
Anorexia (grade 3, 33.3%)
AEs leading to
discontinuation/dose reduction:
Cystitis (grade 2, 33.3%)
Macular edema (grade 2, 33.3%)
Sources: Page: p.533, 536
210.7 mg/m2 1 times / 2 days multiple, oral
MTD
Dose: 210.7 mg/m2, 1 times / 2 days
Route: oral
Route: multiple
Dose: 210.7 mg/m2, 1 times / 2 days
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
150.5 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 150.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 150.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
DLT: ALT increased, Night blindness...
Dose limiting toxicities:
ALT increased (grade 3, 33.3%)
Night blindness (grade 3, 33.3%)
Gamma-glutamyltransferase increased (grade 3, 33.3%)
AST increased (grade 3, 33.3%)
Visual impairment (grade 3, 33.3%)
Sources: Page: p.533, 536
AEs

AEs

AESignificanceDosePopulation
Febrile neutropenia grade 3, 20%
DLT
295 mg/m2 1 times / 2 days multiple, oral
Highest studied dose
Dose: 295 mg/m2, 1 times / 2 days
Route: oral
Route: multiple
Dose: 295 mg/m2, 1 times / 2 days
Sources: Page: p.533, 534, 536
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.533, 534, 536
Platelet count decreased grade 3, 20%
DLT
295 mg/m2 1 times / 2 days multiple, oral
Highest studied dose
Dose: 295 mg/m2, 1 times / 2 days
Route: oral
Route: multiple
Dose: 295 mg/m2, 1 times / 2 days
Sources: Page: p.533, 534, 536
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.533, 534, 536
Anemia grade 3, 20%
Disc. AE
295 mg/m2 1 times / 2 days multiple, oral
Highest studied dose
Dose: 295 mg/m2, 1 times / 2 days
Route: oral
Route: multiple
Dose: 295 mg/m2, 1 times / 2 days
Sources: Page: p.533, 534, 536
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.533, 534, 536
Pneumonia grade 4, 20%
DLT, Disc. AE
295 mg/m2 1 times / 2 days multiple, oral
Highest studied dose
Dose: 295 mg/m2, 1 times / 2 days
Route: oral
Route: multiple
Dose: 295 mg/m2, 1 times / 2 days
Sources: Page: p.533, 534, 536
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.533, 534, 536
Respiratory failure grade 4, 20%
DLT, Disc. AE
295 mg/m2 1 times / 2 days multiple, oral
Highest studied dose
Dose: 295 mg/m2, 1 times / 2 days
Route: oral
Route: multiple
Dose: 295 mg/m2, 1 times / 2 days
Sources: Page: p.533, 534, 536
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.533, 534, 536
Septic shock grade 4, 20%
DLT, Disc. AE
295 mg/m2 1 times / 2 days multiple, oral
Highest studied dose
Dose: 295 mg/m2, 1 times / 2 days
Route: oral
Route: multiple
Dose: 295 mg/m2, 1 times / 2 days
Sources: Page: p.533, 534, 536
unhealthy, ADULT
n = 5
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 5
Sources: Page: p.533, 534, 536
Cystitis grade 2, 33.3%
Disc. AE
107.5 mg/m2 1 times / day multiple, oral
MTD
Dose: 107.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 107.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
Macular edema grade 2, 33.3%
Disc. AE
107.5 mg/m2 1 times / day multiple, oral
MTD
Dose: 107.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 107.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
Anorexia grade 3, 33.3%
DLT, Disc. AE
107.5 mg/m2 1 times / day multiple, oral
MTD
Dose: 107.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 107.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
ALT increased grade 3, 33.3%
DLT
150.5 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 150.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 150.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
AST increased grade 3, 33.3%
DLT
150.5 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 150.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 150.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
Gamma-glutamyltransferase increased grade 3, 33.3%
DLT
150.5 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 150.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 150.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
Visual impairment grade 3, 33.3%
DLT
150.5 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 150.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 150.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
Night blindness grade 3, 33.3%
DLT, Disc. AE
150.5 mg/m2 1 times / day multiple, oral
Studied dose
Dose: 150.5 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 150.5 mg/m2, 1 times / day
Sources: Page: p.533, 536
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.533, 536
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

TAS-116 at 14.0 mg/kg/day was orally administered five times a week for four weeks
Route of Administration: Oral
3 umol/L of TAS-116 does not inhibit GRP94, whereas 0.3 umol/L of TAS-116 inhibits HSP90a and b in HCT116 cells.
Substance Class Chemical
Created
by admin
on Sat Jun 26 07:03:33 UTC 2021
Edited
by admin
on Sat Jun 26 07:03:33 UTC 2021
Record UNII
PLO044MUDZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TAS-116
Preferred Name English
PIMITESPIB
INN  
Official Name English
PIMITESPIB [INN]
Common Name English
BENZAMIDE, 3-ETHYL-4-(3-(1-METHYLETHYL)-4-(4-(1-METHYL-1H-PYRAZOL-4-YL)-1H-IMIDAZOL-1-YL)-1H-PYRAZOLO(3,4-B)PYRIDIN-1-YL)-
Systematic Name English
PIMITESPIB [WHO-DD]
Common Name English
3-ETHYL-4-(3-(1-METHYLETHYL)-4-(4-(1-METHYL-1H-PYRAZOL-4-YL)-1H-IMIDAZOL-1-YL)-1H-PYRAZOLO(3,4-B)PYRIDIN-1-YL)BENZAMIDE
Systematic Name English
Code System Code Type Description
NCI_THESAURUS
C134448
Created by admin on Sat Jun 26 07:03:33 UTC 2021 , Edited by admin on Sat Jun 26 07:03:33 UTC 2021
PRIMARY
DRUG BANK
DB14876
Created by admin on Sat Jun 26 07:03:33 UTC 2021 , Edited by admin on Sat Jun 26 07:03:33 UTC 2021
PRIMARY
MANUFACTURER PRODUCT INFORMATION
TAS-116
Created by admin on Sat Jun 26 07:03:33 UTC 2021 , Edited by admin on Sat Jun 26 07:03:33 UTC 2021
PRIMARY Description: TAS-116 showed activity against orthotopically transplanted NCI-H1975 lung tumors. Together, these data suggest that TAS-116 has a potential to maximize antitumor activity while minimizing adverse effects such as visual disturbances that are observed with other compounds of this class. For the detailed information of TAS-116, the solubility of TAS-116 in water, the solubility of TAS-116 in DMSO, the solubility of TAS-116 in PBS buffer, the animal experiment (test) of TAS-116, the cell expriment (test) of TAS-116, the in vivo, in vitro and clinical trial test of TAS-116, the EC50, IC50, and affinity, of TAS-116, For the detailed information of TAS-116, the solubility of TAS-116 in water, the solubility of TAS-116 in DMSO, the solubility of TAS-116 in PBS buffer, the animal experiment (test) of TAS-116, the cell expriment (test) of TAS-116, the in vivo, in vitro and clinical trial test of TAS-116, the EC50, IC50, and affinity, of TAS-116, Please contact DC Chemicals.
PUBCHEM
67501411
Created by admin on Sat Jun 26 07:03:33 UTC 2021 , Edited by admin on Sat Jun 26 07:03:33 UTC 2021
PRIMARY
FDA UNII
PLO044MUDZ
Created by admin on Sat Jun 26 07:03:33 UTC 2021 , Edited by admin on Sat Jun 26 07:03:33 UTC 2021
PRIMARY
CAS
1260533-36-5
Created by admin on Sat Jun 26 07:03:33 UTC 2021 , Edited by admin on Sat Jun 26 07:03:33 UTC 2021
PRIMARY
INN
11079
Created by admin on Sat Jun 26 07:03:33 UTC 2021 , Edited by admin on Sat Jun 26 07:03:33 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
Oral administration of TAS-116 led to tumor shrinkage in human tumor xenograft mouse models accompanied by depletion of multiple HSP90 clients, demonstrating that the inhibition of HSP90.ALPHA. and .BETA. alone was sufficient to exert antitumor activity in certain tumor models. One of the most notable HSP90-related adverse events universally observed to differing degrees in the clinical setting is visual disturbance. A two-week administration of the isoxazole resorcinol NVP-AUY922, an HSP90 inhibitor, caused marked degeneration and disarrangement of the outer nuclear layer of the retina and induced photoreceptor cell death in rats. In contrast, TAS-116 did not produce detectable photoreceptor injury in rats, probably due to its lower distribution in retinal tissue. Importantly, in a rat model, the antitumor activity of TAS-116 was accompanied by a higher distribution of the compound in subcutaneously xenografted NCI-H1975 non-small cell lung carcinoma tumors than in retina. Moreover, TAS-116 showed activity against orthotopically transplanted NCI-H1975 lung tumors.