VALSPODAR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C63H111N11O12
Molecular Weight	1214.6219
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C\C=C\C[C@@H](C)C(=O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@@H](NC1=O)C(C)C)C(C)C

InChI

InChIKey=YJDYDFNKCBANTM-QCWCSKBGSA-N

InChI=1S/C63H111N11O12/c1-26-27-28-41(16)53(76)52-57(80)67-49(38(10)11)61(84)68(19)33-48(75)69(20)44(29-34(2)3)56(79)66-50(39(12)13)62(85)70(21)45(30-35(4)5)55(78)64-42(17)54(77)65-43(18)58(81)71(22)46(31-36(6)7)59(82)72(23)47(32-37(8)9)60(83)73(24)51(40(14)15)63(86)74(52)25/h26-27,34-47,49-52H,28-33H2,1-25H3,(H,64,78)(H,65,77)(H,66,79)(H,67,80)/b27-26+/t41-,42+,43-,44+,45+,46+,47+,49+,50+,51+,52+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C63H111N11O12
Molecular Weight	1214.6219
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	11 / 11
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18509179
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00002878 | https://clinicaltrials.gov/ct2/show/NCT00002826 | https://clinicaltrials.gov/ct2/show/NCT00004217 | https://clinicaltrials.gov/ct2/show/NCT00006363 | https://www.ncbi.nlm.nih.gov/pubmed/10820137

Valspodar (PSC-833) is a derivative of cyclosporin but devoid of the immunosuppressive and nephrotoxic properties seen in cyclosporin A. It exhibited high-affinity binding to Mdr1 P-glycoprotein (P-gp) and demonstrated multidrug resistance-reversing activity superior to cyclosporin A and verapamil both in vitro and in vivo. Preclinical and phase I/II clinical data have indicated that plasma levels of PSC-833 with multidrug resistance-reversing activities are achievable. Potent inhibition of intestinal, hepatobiliary and blood-brain barrier P-gp function has been demonstrated. The toxicity profiles of valspodar are acceptable and dose-limited by transient and reversible cerebellar ataxia. It has shown multidrug resistance-modulating activities towards acute myeloid leukemia, multiple myeloma and ovarian cancer in phase I/II clinical trials. However, the company discontinued development of valspodar in April 2001 following disappointing results reported from several multicentre phase III studies.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
P-glycoprotein 1 54 Target ID: CHEMBL4302 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10820137	Inhibitor 8297	110.0 nM [IC50]
P-glycoprotein 3 1 Target ID: CHEMBL2573 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17045309	Inhibitor 8297
Multidrug resistance-associated protein 4 14 Target ID: CHEMBL1743128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12036927	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT00002826	Primary	Phase II 1132	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT00002878	Primary	Phase III 656	Unknown Approved Use Unknown
Leukemia 87 Sources: https://clinicaltrials.gov/ct2/show/NCT00004217	Primary	Phase II 1132	Unknown Approved Use Unknown
Adult erythroleukemia 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00006363	Primary	Phase III 656	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-4232	http://www.3bsc.com/index/pro_info.php?id=79172
AA Blocks	AA00158V	https://www.aablocks.com/goods/Goods/detail?id=AA00158V
AHH Chemical co.,ltd	MT-49652	http://www.ahhchemical.com/product/MT-49652.html
AK Scientific, Inc. (AKSCI)	X5944	http://www.aksci.com/item_detail.php?cat=X5944
AbMole Bioscience	M6267	http://www.abmole.com/products/valspodar.html
Achemtek	0102-014578	http://www.achemtek.com/121584-18-7
Active Biopharma	ABP000726	http://www.activebiopharma.com/121584-18-7
Adooq BioScience	PSC-833	http://www.adooq.com/psc-833.html
Adooq BioScience	A11080	https://www.adooq.com/psc-833.html
ApexBio Technology	B5915	http://www.apexbt.com/cyclosporin-d.html
ApexBio Technology	A3905	http://www.apexbt.com/valspodar.html
Aurora Fine Chemicals LLC	A18.034.302	http://online.aurorafinechemicals.com/info?ID=A18.034.302
BLD Pharm	BD156304	http://www.bldpharm.com/products/121584-18-7.html
BOC Sciences	63775-96-2	https://www.bocsci.com/cyclosporin-d-cas-63775-96-2-item-74129.html
BioCrick	BCC2027	http://www.biocrick.com/Valspodar-BCC2027.html
BioSynth	J-004540	https://www.biosynth.com/en/products/all-products/products/J-004540.html
BioSynth	J-525155	https://www.biosynth.com/en/products/all-products/products/J-525155.html
BioSynth	Q-100733	https://www.biosynth.com/en/products/life-science/enzyme-substrates-reagents/products/Q-100733.html
Boerchem	BC638767	http://www.boerchem.com/?product_42952.html
CSNpharm	CSN12182	https://www.csnpharm.com/products/valspodar.html
Chem Scene	CS-1074	http://www.chemscene.com/121584-18-7.html
ChemMol	49421166	http://www.chemmol.com/chemmol/49421166.html
Chemspace	CSSB00161189576	https://chem-space.com/CSSB00161189576
DC Chemicals	DC9813	http://www.dcchemicals.com/product_show-Valspodar_PSC833_.html
Excenen	EX-A2242	https://www.excenen.com/searchresultlist.php?id=121584-18-7
Glentham Life Sciences	GP9440	http://www.glentham.com/products/product/GP9440/
Hairui	HR131612	http://www.hairuichem.com/en/product/63775-96-2.html
Lab Network	LN02125450	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN02125450
MedChem Express	HY-17384	https://www.medchemexpress.com/Valspodar.html
MolPort	MolPort-006-069-277	https://www.molport.com/shop/molecule-link/MolPort-006-069-277
MuseChem	I000816	https://www.musechem.com/product/I000816.html
OChem	7912	http://www.ocheminc.com/index.php?act=psearch&pid=775C962
Smolecule	S548822	http://www.smolecule.com/products/s548822
THE BioTek	bt-288229	https://www.thebiotek.com/product/inhibitors/bt-288229
Tocris	4042	https://www.tocris.com/products/psc-833_4042
Yuhao Chemical	RT18546	http://www.chemyuhao.com/121584-18-7.html
abcr GmbH	AB493732	http://www.abcr.com/shop/en/AB493732
eNovation Chemicals	D395213	https://www.enovationchem.com/ProductDetails.asp?ProductID=D395213
eNovation Chemicals	Y0973909	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0973909

PubMed

Title	Date	PubMed
A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance.	2001 May	11350887
Chronic arsenic-exposed human prostate epithelial cells exhibit stable arsenic tolerance: mechanistic implications of altered cellular glutathione and glutathione S-transferase.	2002 Sep 1	12387749
A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia.	2003 Apr	12531223
Effect of PSC 833, an inhibitor of P-glycoprotein on N-methyl-N-nitrosourea induced mammary carcinogenesis in rats.	2004 Mar	14633655
Up-regulation of MDR1 and induction of doxorubicin resistance by histone deacetylase inhibitor depsipeptide (FK228) and ATRA in acute promyelocytic leukemia cells.	2006 Feb 15	16223781
Myricetin stimulates the absorption of the pro-carcinogen PhIP.	2006 Jan 8	16356829
Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein.	2006 Jun	16671962
Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein.	2006 Sep	16810505
Celecoxib enhances doxorubicin-induced cytotoxicity in MDA-MB231 cells by NF-kappaB-mediated increase of intracellular doxorubicin accumulation.	2007 Jan	17097285

Patents

Sample Use Guides

In Vivo Use Guide

2 mg/kg load IV over 2 hrs (loading); 10 mg/kg/day Continuous hours 0 - 96

Route of Administration: Intravenous

In Vitro Use Guide

MDA/T0.3 cells were incubated in 1 mkM PSC-833 for 24 hours and the IC50 of taxol determined in the presence of PSC-833.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 15:52:11 GMT 2023` Edited by `admin` on `Sat Dec 16 15:52:11 GMT 2023`
Record UNII	Q7ZP55KF3X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VALSPODAR

Official Name

English

VALSPODAR [MI]

Common Name

English

valspodar [INN]

Common Name

English

CYCLOSPORIN D, 6-((2S,4R,6E)-4-METHYL-2-METHYLAMINO)-3-OXO-6-OCTENOIC ACID)-

Common Name

English

VALSPODAR [USAN]

Common Name

English

CYCLO(((2S,4R,6E)-4-METHYL-2-(METHYLAMINO)-3-OXO-6-OCTENOYL)-L-VALYL-N-METHYLGLYCYL-N-METHYL-L-LEUCYL-L-VALYL-N-METHYL-L-LEUCYL-L-ALANYL-D-ALANYL-N-METHYL-L-LEUCYL-N-METHYL-L-LEUCYL-N-METHYL-L-VALYL)

Common Name

English

VALSPODAR [VANDF]

Common Name

English

SDZ PSC 833

Code

English

VALSPODAR [MART.]

Common Name

English

SDZ-PSC 833

Code

English

Valspodar [WHO-DD]

Common Name

English

AMDRAY

Brand Name

English

PSC833

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1744