CUDC-101

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H26N4O4
Molecular Weight	434.4876
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(C=C1OCCCCCCC(=O)NO)C(NC3=CC(=CC=C3)C#C)=NC=N2

InChI

InChIKey=PLIVFNIUGLLCEK-UHFFFAOYSA-N

InChI=1S/C24H26N4O4/c1-3-17-9-8-10-18(13-17)27-24-19-14-22(21(31-2)15-20(19)25-16-26-24)32-12-7-5-4-6-11-23(29)28-30/h1,8-10,13-16,30H,4-7,11-12H2,2H3,(H,28,29)(H,25,26,27)

HIDE SMILES / InChI

Molecular Formula	C24H26N4O4
Molecular Weight	434.4876
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20388807
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25940539 http://investors.curis.com/secfiling.cfm?filingid=1193125-14-97662&cik=1108205

CUDC-101 is a multi-targeted agent designed to inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor Type 2 (Her2) and histone deacetylase (HDAC). This drug synergistically blocked key regulators of EGFR/HER2 signaling pathways, also attenuating multiple compensatory pathways, such as AKT, HER3, and MET, which enable cancer cells to escape the effects of conventional EGFR/HER2 inhibitors. Thus, a single compound may offer greater therapeutic benefits, which is verified in clinical trial phase I for the treatment patients with advanced head and neck, gastric, breast, liver, and non-small cell lung cancer tumors. In April 2013, CURIS, INC determined that they would discontinue enrolling patients in phase 1 expansion trial of the intravenous formulation of CUDC-101, and that the future development of CUDC-101 would be dependent on our ability to successfully develop an oral formulation of CUDC-101. However, the efforts to develop an effective oral formulation with improved bioavailability have not resulted in significant improvements when compared to the intravenous formulation of CUDC-101. As a result, at this time CURIS no longer plan to make material investments in this program.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histone deacetylase 23 Target ID: CHEMBL2093865 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20143778	Inhibitor 8297	4.4 nM [IC50]
Epidermal growth factor receptor erbB1 58 Target ID: CHEMBL203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20143778	Inhibitor 8297	2.4 nM [IC50]
Receptor protein-tyrosine kinase erbB-2 35 Target ID: CHEMBL1824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20143778	Inhibitor 8297	15.7 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Head and neck cancer 50 Sources: https://clinicaltrials.gov/ct2/show/NCT01171924	Primary	Phase I 428	Unknown Approved Use Unknown
Liver cancer 53 Sources: https://clinicaltrials.gov/ct2/show/NCT01171924	Primary	Phase I 428	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT01171924	Primary	Phase I 428	Unknown Approved Use Unknown
Gastric cancer 53 Sources: https://clinicaltrials.gov/ct2/show/NCT01171924	Primary	Phase I 428	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT01171924	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
8.83 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25107918	300 mg 1 times / day multiple, intravenous dose: 300 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		CUDC-101 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.23 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25107918	275 mg 1 times / day multiple, intravenous dose: 275 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		CUDC-101 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
10.6 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25107918	300 mg 1 times / day multiple, intravenous dose: 300 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		CUDC-101 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.99 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25107918	275 mg 1 times / day multiple, intravenous dose: 275 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		CUDC-101 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25107918	300 mg 1 times / day multiple, intravenous dose: 300 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		CUDC-101 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25107918	275 mg 1 times / day multiple, intravenous dose: 275 mg route of administration: Intravenous experiment type: MULTIPLE co-administered:		CUDC-101 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116321	https://www.001chemical.com/chem/search?q=DY116321
1PlusChem LLC	1P0004EX	https://www.1pchem.com/search?query=1P0004EX
A2B Chem	AA04921	http://a2bchem.com/prod/AA04921
AChemBlock	10307	http://www.achemblock.com/catalogsearch/result/?q=10307
AK Scientific	X7526	https://aksci.com/item_detail.php?cat=X7526
AOBIOUS INC	AOB6495	http://aobious.com/aobious/search?search_query=AOB6495
Ambeed	A165599	http://www.ambeed.com/search/Search.html?keyword=A165599
Angene	AGN-PC-04QQ59	http://www.angenechemical.com/productshow/AGN-PC-04QQ59.html
ApexBio Technology	A4092	https://www.apexbt.com/catalogsearch/result/?q=A4092
AstaTech	42007	http://astatechinc.com/CPSResult.php?CRNO=42007
BLD Pharm	BD304693	http://www.bldpharm.com/search/Search.html?keyword=BD304693
BOC Sciences	1012054-59-9	http://www.bocsci.com/description.asp?cas=1012054-59-9
Capot Chemical	19149	https://www.capotchem.com/search.do?q=19149
Cayman Chemical	16426	http://www.caymanchem.com/app/template/Product.vm/catalog/16426
Chem Scene	CS-0038	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0038
ChemShuttle	104818	https://www.chemshuttle.com/catalogsearch/result/?q=104818
Excenen	EX-A842	http://www.excenen.com/searchresultlist.php?id=EX-A842
Fluorochem	50687	http://www.fluorochem.co.uk/Products/Product?code=050687
KeyOrganics	AS-16955	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16955
Matrix Scientific	145212	http://www.matrixscientific.com/145212.html
MedChem Express	HY-10223	https://www.medchemexpress.com/search.html?q=HY-10223&ft=&fa=&fp=
MolPort	MolPort-009-679-462	https://www.molport.com/shop/molecule-link/MolPort-009-679-462
Molcore	MC116321	http://www.molcore.com/CatMC116321.html
Molnova	M10074	https://www.molnova.com/en/serch-list.html?keywords=M10074
MuseChem	I000119	https://www.musechem.com/product/I000119.html
ShangHai Biochempartner	BCP000197	http://www.biochempartner.com/search_BCP000197
ShangHai Biochempartner	BCP01935	http://www.biochempartner.com/search_BCP01935
TargetMol	T3108	https://www.targetmol.com/search?keyword=T3108
Toronto Research Chemicals	C834500	https://www.trc-canada.com/product-detail/?CatNum=C834500
Toronto Research Chemicals	M313457	https://www.trc-canada.com/product-detail/?CatNum=M313457
eMolecules	32176513	https://orderbb.emolecules.com/search/#?query=32176513
eNovation Chemicals	D501877	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501877&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6930498263	https://mcule.com/MCULE-6930498263/

PubMed

Title	Date	PubMed
CUDC-101, a multitargeted inhibitor of histone deacetylase, epidermal growth factor receptor, and human epidermal growth factor receptor 2, exerts potent anticancer activity.	2010 May 1	20388807
Phase I first-in-human study of CUDC-101, a multitargeted inhibitor of HDACs, EGFR, and HER2 in patients with advanced solid tumors.	2014 Oct 1	25107918
A Phase I Study of CUDC-101, a Multitarget Inhibitor of HDACs, EGFR, and HER2, in Combination with Chemoradiation in Patients with Head and Neck Squamous Cell Carcinoma.	2015 Apr 1	25573383

Patents

Sample Use Guides

In Vivo Use Guide

CUDC-101 administered as a 1 hour intravenous infusion at the maximum tolerated dose of 275 mg/m2 on Monday, Wednesday, Friday for three consecutive weeks of each 28 day cycle.

Route of Administration: Intravenous

In Vitro Use Guide

Anaplastic thyroid cancer (ATC) cells were treated with the vehicle or CUDC-101 at 1.1 μM for 24 hour. CUDC-101 inhibited MAPK signaling and histone deacetylation in ATC cell lines with multiple driver mutations present in human ATC. The anticancer effect of CUDC-101 was associated with increased expression of p21 and E-cadherin, and reduced expression of survivin, XIAP, β-catenin, N-cadherin, and Vimentin.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:11:03 GMT 2023` Edited by `admin` on `Sat Dec 16 05:11:03 GMT 2023`
Record UNII	1A7Y9MP123
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CUDC-101

Common Name

English

7-((4-(3-ETHYNYLPHENYLAMINO)-7-METHOXYQUINAZOLIN-6-YL)OXY)-N-HYDROXYHEPTANAMIDE

Systematic Name

English

CUDC 101 [WHO-DD]

Common Name

English

Code System Code Type Description

FDA UNII

1A7Y9MP123