VALSPODAR

Investigational

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 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	1214.6244
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 8504	110.0 nM [IC50]
P-glycoprotein 3 1 Target ID: CHEMBL2573 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17045309	Inhibitor 8504
Multidrug resistance-associated protein 4 14 Target ID: CHEMBL1743128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12036927	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 432 Sources: https://clinicaltrials.gov/ct2/show/NCT00002826	Primary	Phase II 1147	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT00002878	Primary	Phase III 665	Unknown Approved Use Unknown
Leukemia 72 Sources: https://clinicaltrials.gov/ct2/show/NCT00004217	Primary	Phase II 1147	Unknown Approved Use Unknown
Adult erythroleukemia 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00006363	Primary	Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
2495 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11223552	8 mg/kg 1 times / 3 weeks steady-state, intravenous dose: 8 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered: Doxorubicin	Doxorubicin	VALSPODAR blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.3 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9855321	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		VALSPODAR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
58.2 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11223552	8 mg/kg 1 times / 3 weeks steady-state, intravenous dose: 8 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered: Doxorubicin	Doxorubicin	VALSPODAR blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.8 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9855321	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		VALSPODAR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
24.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9855321	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		VALSPODAR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

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
abcr GmbH	AB493732	http://www.abcr.com/shop/en/AB493732
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	A11080	https://www.adooq.com/psc-833.html
Adooq BioScience	PSC-833	http://www.adooq.com/psc-833.html
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
ApexBio Technology	A3905	http://www.apexbt.com/valspodar.html
ApexBio Technology	B5915	http://www.apexbt.com/cyclosporin-d.html
Aurora Fine Chemicals LLC	A18.034.302	http://online.aurorafinechemicals.com/info?ID=A18.034.302
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
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
Boerchem	BC638767	http://www.boerchem.com/?product_42952.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
CSNpharm	CSN12182	https://www.csnpharm.com/products/valspodar.html
DC Chemicals	DC9813	http://www.dcchemicals.com/product_show-Valspodar_PSC833_.html
eNovation Chemicals	D395213	https://www.enovationchem.com/ProductDetails.asp?ProductID=D395213
eNovation Chemicals	Y0973909	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0973909
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

PubMed

Title	Date	PubMed
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.	2015-01-05	25466967
Multi-drug resistance in a canine lymphoid cell line due to increased P-glycoprotein expression, a potential model for drug-resistant canine lymphoma.	2014-12	24975508
MDR1 transporter protects against paraquat-induced toxicity in human and mouse proximal tubule cells.	2014-10	25015657
Nickel-induced cell death and survival pathways in cultured renal proximal tubule cells: roles of reactive oxygen species, ceramide and ABCB1.	2014-04	24448832
Optimization of irinotecan chronotherapy with P-glycoprotein inhibition.	2014-02-01	24380837
Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux.	2012-05-01	22464980
Synthesis and structure-activity evaluation of isatin-β-thiosemicarbazones with improved selective activity toward multidrug-resistant cells expressing P-glycoprotein.	2011-08-25	21721528
ABCB1 protects kidney proximal tubule cells against cadmium-induced apoptosis: roles of cadmium and ceramide transport.	2011-06	21436125
Interaction of anthelmintic drugs with P-glycoprotein in recombinant LLC-PK1-mdr1a cells.	2010-08-05	20513441
Epigenetic mechanisms involved in differential MDR1 mRNA expression between gastric and colon cancer cell lines and rationales for clinical chemotherapy.	2008-08-01	18673531
Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells.	2008-01	17947497
Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship.	2007-01	17134887
Celecoxib enhances doxorubicin-induced cytotoxicity in MDA-MB231 cells by NF-kappaB-mediated increase of intracellular doxorubicin accumulation.	2007-01	17097285
Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein.	2006-09	16810505
Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein.	2006-06	16671962
Effect of organophosphate pesticide diazinon on expression and activity of intestinal P-glycoprotein.	2006-03-01	16221533
Up-regulation of MDR1 and induction of doxorubicin resistance by histone deacetylase inhibitor depsipeptide (FK228) and ATRA in acute promyelocytic leukemia cells.	2006-02-15	16223781
Myricetin stimulates the absorption of the pro-carcinogen PhIP.	2006-01-08	16356829
Cyclosporin A is a broad-spectrum multidrug resistance modulator.	2005-03-15	15788683
Reversal of multidrug-resistance using Valspodar (PSC 833) and doxorubicin in osteosarcoma.	2004-11	15492788
ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages.	2004-08	15456083
Effect of PSC 833, an inhibitor of P-glycoprotein on N-methyl-N-nitrosourea induced mammary carcinogenesis in rats.	2004-03	14633655
Examination of the functional activity of P-glycoprotein in the rat placental barrier using rhodamine 123.	2003-06	12626638
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.	2003-04	12531223
Chronic arsenic-exposed human prostate epithelial cells exhibit stable arsenic tolerance: mechanistic implications of altered cellular glutathione and glutathione S-transferase.	2002-09-01	12387749
Stereoselective transport of hydrophilic quaternary drugs by human MDR1 and rat Mdr1b P-glycoproteins.	2002-04	11934808
Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic.	2001-08	11455017
A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance.	2001-05	11350887
Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein inhibitor valspodar and mitotane or doxorubicin.	2000-04	10898547
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.	2000-01-21	10636889
Cyclosporin analogs inhibit in vitro growth of Cryptosporidium parvum.	1998-04	9559794
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.	1997-09	9303374
A patient with adrenocortical carcinoma: characterization of its biological activity and drug resistance profile.	1997-03	9815696

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 `Wed Apr 02 06:53:07 GMT 2025` Edited by `admin` on `Wed Apr 02 06:53:07 GMT 2025`
Record UNII	Q7ZP55KF3X
Record Status	`FAILED`
Record Version

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Name

Type

Language

VALSPODAR

Official Name

English

AMDRAY

Preferred 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

PSC833

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1744