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Details

Stereochemistry ABSOLUTE
Molecular Formula C63H111N11O12
Molecular Weight 1214.6244
Optical Activity UNSPECIFIED
Defined Stereocenters 11 / 11
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of VALSPODAR

SMILES

C/C(/[H])=C(\[H])/C[C@@]([H])(C)C(=O)[C@@]1([H])C(=N[C@@]([H])(C(C)C)C(=O)N(C)CC(=O)N(C)[C@@]([H])(CC(C)C)C(=N[C@@]([H])(C(C)C)C(=O)N(C)[C@@]([H])(CC(C)C)C(=N[C@@]([H])(C)C(=N[C@]([H])(C)C(=O)N(C)[C@@]([H])(CC(C)C)C(=O)N(C)[C@@]([H])(CC(C)C)C(=O)N(C)[C@@]([H])(C(C)C)C(=O)N1C)O)O)O)O

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 1214.6244
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 11 / 11
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
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

Curator's Comment:: Also known to be CNS penetrant in mouse

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
A patient with adrenocortical carcinoma: characterization of its biological activity and drug resistance profile.
1997 Mar
Characterization of anti-Toxoplasma activity of SDZ 215-918, a cyclosporin derivative lacking immunosuppressive and peptidyl-prolyl-isomerase-inhibiting activity: possible role of a P glycoprotein in Toxoplasma physiology.
1997 Sep
Cyclosporin analogs inhibit in vitro growth of Cryptosporidium parvum.
1998 Apr
Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein inhibitor valspodar and mitotane or doxorubicin.
2000 Apr
Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappaB activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis.
2000 Jan 21
Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic.
2001 Aug
A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance.
2001 May
Stereoselective transport of hydrophilic quaternary drugs by human MDR1 and rat Mdr1b P-glycoproteins.
2002 Apr
Chronic arsenic-exposed human prostate epithelial cells exhibit stable arsenic tolerance: mechanistic implications of altered cellular glutathione and glutathione S-transferase.
2002 Sep 1
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
Examination of the functional activity of P-glycoprotein in the rat placental barrier using rhodamine 123.
2003 Jun
ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages.
2004 Aug
Effect of PSC 833, an inhibitor of P-glycoprotein on N-methyl-N-nitrosourea induced mammary carcinogenesis in rats.
2004 Mar
Reversal of multidrug-resistance using Valspodar (PSC 833) and doxorubicin in osteosarcoma.
2004 Nov
Cyclosporin A is a broad-spectrum multidrug resistance modulator.
2005 Mar 15
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
Myricetin stimulates the absorption of the pro-carcinogen PhIP.
2006 Jan 8
Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein.
2006 Jun
Effect of organophosphate pesticide diazinon on expression and activity of intestinal P-glycoprotein.
2006 Mar 1
Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein.
2006 Sep
Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship.
2007 Jan
Celecoxib enhances doxorubicin-induced cytotoxicity in MDA-MB231 cells by NF-kappaB-mediated increase of intracellular doxorubicin accumulation.
2007 Jan
Epigenetic mechanisms involved in differential MDR1 mRNA expression between gastric and colon cancer cell lines and rationales for clinical chemotherapy.
2008 Aug 1
Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells.
2008 Jan
Interaction of anthelmintic drugs with P-glycoprotein in recombinant LLC-PK1-mdr1a cells.
2010 Aug 5
Synthesis and structure-activity evaluation of isatin-β-thiosemicarbazones with improved selective activity toward multidrug-resistant cells expressing P-glycoprotein.
2011 Aug 25
ABCB1 protects kidney proximal tubule cells against cadmium-induced apoptosis: roles of cadmium and ceramide transport.
2011 Jun
Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux.
2012 May 1
Nickel-induced cell death and survival pathways in cultured renal proximal tubule cells: roles of reactive oxygen species, ceramide and ABCB1.
2014 Apr
Multi-drug resistance in a canine lymphoid cell line due to increased P-glycoprotein expression, a potential model for drug-resistant canine lymphoma.
2014 Dec
Optimization of irinotecan chronotherapy with P-glycoprotein inhibition.
2014 Feb 1
MDR1 transporter protects against paraquat-induced toxicity in human and mouse proximal tubule cells.
2014 Oct
Expression of drug transporters and drug metabolizing enzymes in the bladder urothelium in man and affinity of the bladder spasmolytic trospium chloride to transporters likely involved in its pharmacokinetics.
2015 Jan 5
Patents

Patents

Sample Use Guides

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 Fri Jun 25 23:28:49 UTC 2021
Edited
by admin
on Fri Jun 25 23:28:49 UTC 2021
Record UNII
Q7ZP55KF3X
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VALSPODAR
INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
VALSPODAR [MI]
Common Name English
VALSPODAR [INN]
Common Name English
VALSPODAR [WHO-DD]
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
AMDRAY
Brand Name English
PSC 833
Code English
Classification Tree Code System Code
NCI_THESAURUS C1744
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
Code System Code Type Description
CAS
121584-18-7
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
NCI_THESAURUS
C1405
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
EVMPD
SUB00018MIG
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
FDA UNII
Q7ZP55KF3X
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
MERCK INDEX
M11373
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY Merck Index
INN
7481
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
DRUG BANK
DB11869
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
MESH
C070272
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
PUBCHEM
5281884
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
ChEMBL
CHEMBL1086218
Created by admin on Fri Jun 25 23:28:49 UTC 2021 , Edited by admin on Fri Jun 25 23:28:49 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
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ACTIVE MOIETY