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
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
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/18509179Curator'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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15110893
Curator's Comment: Also known to be CNS penetrant in mouse
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4302 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10820137 |
110.0 nM [IC50] | ||
Target ID: CHEMBL2573 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17045309 |
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Target ID: CHEMBL1743128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12036927 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance. | 2001 May |
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Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein. | 2006 Jun |
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Effect of organophosphate pesticide diazinon on expression and activity of intestinal P-glycoprotein. | 2006 Mar 1 |
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Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. | 2008 Jan |
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Interaction of anthelmintic drugs with P-glycoprotein in recombinant LLC-PK1-mdr1a cells. | 2010 Aug 5 |
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Optimization of irinotecan chronotherapy with P-glycoprotein inhibition. | 2014 Feb 1 |
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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
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00004217
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9770112
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.
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NCI_THESAURUS |
C1744
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C1405
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7481
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Valspodar
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CHEMBL1086218
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MM-11
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ACTIVE MOIETY