TENALISIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H18FN5O2
Molecular Weight	415.4197
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC[C@H](NC1=C2N=CNC2=NC=N1)C3=C(C(=O)C4=C(O3)C=CC=C4)C5=CC(F)=CC=C5

InChI

InChIKey=HDXDQPRPFRKGKZ-INIZCTEOSA-N

InChI=1S/C23H18FN5O2/c1-2-16(29-23-19-22(26-11-25-19)27-12-28-23)21-18(13-6-5-7-14(24)10-13)20(30)15-8-3-4-9-17(15)31-21/h3-12,16H,2H2,1H3,(H2,25,26,27,28,29)/t16-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C23H18FN5O2
Molecular Weight	415.4197
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.bloodjournal.org/content/122/21/4411?sso-checked=true | http://cancerres.aacrjournals.org/content/75/15_Supplement/2704 | http://adisinsight.springer.com/drugs/800039373

RP6530 (Tenalisib) is a potent and selective dual Phosphatidylinositol 3 kinase (PI3K) δ/γ inhibitor. It inhibited growth of B-cell lymphoma cell lines, additionally, the compound showed cytotoxicity in a panel of lymphoma primary cells. Rhizen Pharmaceuticals is developing RP6530 for the treatment of hematologic malignancies.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: http://www.bloodjournal.org/content/122/21/4411?sso-checked=true	Inhibitor 8297		24.5 nM [IC50]
PI3-kinase p110-gamma subunit 32 Target ID: CHEMBL3267 Sources: http://www.bloodjournal.org/content/122/21/4411?sso-checked=true	Inhibitor 8297		33.2 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Lymphoma, T-cell, peripheral 2 Sources: http://adisinsight.springer.com/drugs/800039373	Primary	Phase I 428	Unknown Approved Use Unknown
Cutaneous T-cell lymphoma 9 Sources: http://adisinsight.springer.com/drugs/800039373	Primary	Phase I 428	Unknown Approved Use Unknown
B-cell lymphoma 3 Sources: http://adisinsight.springer.com/drugs/800039373	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
3100.66 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	600 mg 3 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5692.04 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	800 mg 3 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4508.55 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5777.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3521.29 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3510.58 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1383.32 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1525.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
22282.67 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	600 mg 3 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
37313.58 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	800 mg 3 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
16214.14 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
21261.13 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
25631.93 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
26627.57 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5173.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8268.96 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
3.89 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	1200 mg 2 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.49 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5.09 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.51 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.33 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31761713/	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TENALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P01ENL3	https://www.1pchem.com/search?query=1P01ENL3
AChemBlock	K13499	http://www.achemblock.com/catalogsearch/result/?q=K13499
AstaTech	C73162	http://astatechinc.com/CPSResult.php?CRNO=C73162
Chem Scene	CS-6375	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-6375
Excenen	EX-A2699	http://www.excenen.com/searchresultlist.php?id=EX-A2699
KeyOrganics	AS-56118	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56118
MedChem Express	HY-17645	https://www.medchemexpress.com/search.html?q=HY-17645&ft=&fa=&fp=
MolPort	MolPort-046-418-347	https://www.molport.com/shop/molecule-link/MolPort-046-418-347
MolPort	MolPort-046-702-242	https://www.molport.com/shop/molecule-link/MolPort-046-702-242
MuseChem	I009750	https://www.musechem.com/product/I009750.html
Selleck Chemicals	S8672	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8672
ShangHai Biochempartner	BCP25998	http://www.biochempartner.com/search_BCP25998
eMolecules	266610585	https://orderbb.emolecules.com/search/#?query=266610585
eMolecules	295312065	https://orderbb.emolecules.com/search/#?query=295312065
eMolecules	76742422	https://orderbb.emolecules.com/search/#?query=76742422
mcule	MCULE-6502884430	https://mcule.com/MCULE-6502884430/

Sample Use Guides

In Vivo Use Guide

Phase 1 studies for the treatment of hematologic malignancies: RP6530 administered orally twice a day (Tablet starting at 200 mg) or RP6530 administered orally (Escalating doses starting at 25 mg BID)

Route of Administration: Oral

In Vitro Use Guide

While single-agent activity of RP6530 was modest (33-46% inhibition @ 10 μM) in both HEL-RS and HEL-RR cells, addition of 10 μM RP6530 to ruxolitinib was synergistic resulting in a near-complete inhibition of proliferation (>90% for HEL-RS and >70% for HEL-RR). While the order of addition did not affect the potency of RP6530, addition of 5 μM RP6530, 4 h prior to the addition of ruxolitinib resulted in a significant reduction in EC50 of ruxolitinib (5.8 μM) in HEL-RR cells. On lines with cell proliferation data, incubation of 10 μM RP6530 with ruxolitinib for 72 h increased the percent of apoptotic cells (55% in HEL-RS and 37% in HEL-RR) compared to either agent alone (16-27% in HEL-RS and 17-21% in HEL-RR).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:56:36 UTC 2023` Edited by `admin` on `Fri Dec 15 15:56:36 UTC 2023`
Record UNII	2261HH611H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TENALISIB

Official Name

English

3-(3-FLUOROPHENYL)-2-((1S)-1-((7H-PURIN-6-YL)AMINO)PROPYL)-4H-1-BENZOPYRAN-4-ONE

Systematic Name

English

tenalisib [INN]

Common Name

English

Tenalisib [WHO-DD]

Common Name

English

4H-1-BENZOPYRAN-4-ONE, 3-(3-FLUOROPHENYL)-2-((1S)-1-(9H-PURIN-6-YLAMINO)PROPYL)-

Systematic Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

616417