Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C22H19ClN6O2S |
Molecular Weight | 466.943 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@@H]1COC(NC2=CC=C3N=CN=C(NC4=CC(Cl)=C(OCC5=NC=CS5)C=C4)C3=C2)=N1
InChI
InChIKey=UWXSAYUXVSFDBQ-CYBMUJFWSA-N
InChI=1S/C22H19ClN6O2S/c1-13-10-31-22(27-13)29-14-2-4-18-16(8-14)21(26-12-25-18)28-15-3-5-19(17(23)9-15)30-11-20-24-6-7-32-20/h2-9,12-13H,10-11H2,1H3,(H,27,29)(H,25,26,28)/t13-/m1/s1
DescriptionSources: http://investor.arraybiopharma.com/phoenix.zhtml?c=123810&p=irol-newsArticle&ID=1584707Curator's Comment: description was created based on several sources, including
http://www.aslanpharma.com/drug/aslan001/
Sources: http://investor.arraybiopharma.com/phoenix.zhtml?c=123810&p=irol-newsArticle&ID=1584707
Curator's Comment: description was created based on several sources, including
http://www.aslanpharma.com/drug/aslan001/
Varlitinib (Alternative Names: ARRY-334543; ARRY-543; ASLAN-001; Varlitinib tosylate) is a small molecule based reversible pan-HER inhibitor of EGFR, HER2 and HER4. In response to the binding of various ligands, these kinases undergo heterodimerisation and homodimerization, resulting in activation of numerous growth factor signaling pathways, by inhibiting the activation of the HER receptors via drug, effects such as shrinkage of the tumor and longer survival can be anticipated. In a large variety of cancers, the overexpression and/or constitutive activation of EGFR and HER2 are often observed and frequently correlate with poor clinical prognosis. Licensed from Array BioPharma with global rights for all indications, varlitinib is being developed as first-in-class drug for cholangiocarcinoma, gastric and colorectal cancer, and as best-in-class drug for breast cancer.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL203 Sources: http://www.aslanpharma.com/drug/aslan001/ |
36.0 nM [IC50] | ||
Target ID: CHEMBL1824 Sources: http://www.aslanpharma.com/drug/aslan001/ |
43.0 nM [IC50] | ||
Target ID: CHEMBL3009 Sources: http://www.aslanpharma.com/drug/aslan001/ |
132.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse events |
---|---|---|
600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: |
DLT: Thrombosis, AST increased... Dose limiting toxicities: Thrombosis (grade 3, 25%) Sources: AST increased (grade 3, 25%) ALT increased (grade 3, 25%) Anorexia (grade 3, 25%) |
300 mg 2 times / day multiple, oral MTD Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Co-administed with:: 5-fluorouracil Sources: leucovorin irinotecan |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: |
DLT: Stomatitis... Dose limiting toxicities: Stomatitis (grade 3) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
ALT increased | grade 3, 25% DLT |
600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: |
AST increased | grade 3, 25% DLT |
600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: |
Anorexia | grade 3, 25% DLT |
600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: |
Thrombosis | grade 3, 25% DLT |
600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: |
Stomatitis | grade 3 DLT |
300 mg 2 times / day multiple, oral MTD Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Co-administed with:: 5-fluorouracil Sources: leucovorin irinotecan |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: |
Sample Use Guides
starting dose: 300 mg BID (two times a day); target dose: 400 mg BID; dose modification by investigator allowed between 200 mg BID to 500 mg BID
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=24939447
Lung cancer cell line NCI-H460 and its ABCG2-overexpressing NCI-H460/MX20, as well as the ABCG2-, ABCB1-, and ABCC10-overexpressing transfected cell lines were used for the reversal study. ARRY-334543 (VARLITINIB) (1.0 μM) significantly reversed ABCG2-mediated multidrug resistance (MDR) by directly inhibiting the drug efflux function of ABCG2, resulting in the elevated intracellular accumulation of chemotherapeutic drugs in the ABCG2-overexpressing cell lines. In addition, in isolated membranes, ARRY-334543 stimulated ATPase activity and inhibited photolabeling of ABCG2 with [(125)I]-iodoarylazidoprazosin in a concentration-dependent manner indicating that this drug directly interacts at the drug-binding pocket of this transporter. ARRY-334543 (1.0 μM) only slightly reversed ABCB1- and partially reversed ABCC10-mediated MDR suggesting that it exhibits high affinity toward ABCG2.
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C129825
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
||
|
FDA ORPHAN DRUG |
524216
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
||
|
NCI_THESAURUS |
C2167
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
||
|
FDA ORPHAN DRUG |
485915
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
DB05944
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
DTXSID501025597
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
UU-43
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
846Y8197W1
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
100000174734
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
9187
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
C62530
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
845272-21-1
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
CHEMBL2103842
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY | |||
|
42642648
Created by
admin on Fri Dec 15 16:25:34 GMT 2023 , Edited by admin on Fri Dec 15 16:25:34 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)