ZOPTARELIN DOXORUBICIN ACETATE

First approved in 1974

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C91H117N19O26.3C2H4O2
Molecular Weight	2073.1703
Optical Activity	UNSPECIFIED
Defined Stereocenters	15 / 15
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of ZOPTARELIN DOXORUBICIN ACETATE

Structure Search

SMILES

CC(O)=O.CC(O)=O.CC(O)=O.[H][C@@]1(C[C@H](N)[C@H](O)[C@H](C)O1)O[C@H]2C[C@@](O)(CC3=C2C(O)=C4C(=O)C5=C(OC)C=CC=C5C(=O)C4=C3O)C(=O)COC(=O)CCCC(=O)NCCCC[C@@H](NC(=O)[C@H](CC6=CC=C(O)C=C6)NC(=O)[C@H](CO)NC(=O)[C@H](CC7=CNC8=CC=CC=C78)NC(=O)[C@H](CC9=CN=CN9)NC(=O)[C@@H]%10CCC(=O)N%10)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N%11CCC[C@H]%11C(=O)NCC(N)=O

InChI

InChIKey=XBNFJFHLGRBGTL-KICSVHBJSA-N

InChI=1S/C91H117N19O26.3C2H4O2/c1-44(2)31-58(83(125)104-57(17-11-29-98-90(94)95)89(131)110-30-12-18-63(110)88(130)100-40-67(93)114)105-81(123)55(16-7-8-28-97-68(115)20-10-21-70(117)134-42-66(113)91(132)36-52-73(65(37-91)136-71-35-53(92)76(118)45(3)135-71)80(122)75-74(78(52)120)77(119)51-14-9-19-64(133-4)72(51)79(75)121)103-84(126)59(32-46-22-24-49(112)25-23-46)106-87(129)62(41-111)109-85(127)60(33-47-38-99-54-15-6-5-13-50(47)54)107-86(128)61(34-48-39-96-43-101-48)108-82(124)56-26-27-69(116)102-56;3*1-2(3)4/h5-6,9,13-15,19,22-25,38-39,43-45,53,55-63,65,71,76,99,111-112,118,120,122,132H,7-8,10-12,16-18,20-21,26-37,40-42,92H2,1-4H3,(H2,93,114)(H,96,101)(H,97,115)(H,100,130)(H,102,116)(H,103,126)(H,104,125)(H,105,123)(H,106,129)(H,107,128)(H,108,124)(H,109,127)(H4,94,95,98);3*1H3,(H,3,4)/t45-,53-,55+,56-,57-,58-,59-,60-,61-,62-,63-,65-,71-,76+,91-;;;/m0.../s1

HIDE SMILES / InChI

Molecular Formula	C91H117N19O26
Molecular Weight	1893.0144
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	15 / 15
E/Z Centers	6
Optical Activity	UNSPECIFIED

Molecular Formula	C2H4O2
Molecular Weight	60.052
Charge	0
Count

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

Description
Sources: http://www.drugbank.ca/drugs/DB00997http://www.cytrx.com/aldoxorubicin
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/28846045 | https://clinicaltrials.gov/ct2/show/NCT02049905 | https://www.ncbi.nlm.nih.gov/pubmed/26378637 | https://clinicaltrials.gov/ct2/show/NCT02014844 | https://www.ncbi.nlm.nih.gov/pubmed/25312684 | https://clinicaltrials.gov/ct2/show/NCT02200757

Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate developed by CytRx for treating relapsed and refractory sarcomas, especially L-sarcomas. Aldoxorubicin is a rationally-engineered cytotoxic which delivers a well-established anti-cancer agent, doxorubicin, into the tumor. Currently, in late-stage clinical trials, Aldoxorubicin appears to overcome the key limitations of doxorubicin, including cumulative dose restrictions. Aldoxorubicin utilizes an acid-sensitive linker that selectively binds to albumin, which may allow the cytotoxic payload to preferentially accumulate in the tumor and potentially spare the surrounding healthy tissue. This mechanism leverages the tumor's low pH environment and accompanying dependency upon circulating albumin to fuel growth, to enable the delivery of multifold times the standard dosing of doxorubicin. The preferential uptake of Aldoxorubicin by tumor tissue and the acid sensitive release of doxorubicin allow for Aldoxorubicin to be a very promising anticancer agent. In phase I and II trials, Aldoxorubicin demonstrates superior efficacy over doxorubicin. Although the studies were not powered for OS, Aldoxorubicin shows improved PFS and tumor response in comparison to doxorubicin. The safety profile was also comparable to that of doxorubicin. Similarly, results from the recent phase III study showed a benefit in PFS in the leiomyosarcoma subtypes.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28846045	Inhibitor 8297	2.67 µM [IC50]
Serum albumin 18 Target ID: CHEMBL3253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28846045	Binding Agent 1064
DNA topoisomerase II alpha 37 Target ID: CHEMBL1806 Sources: http://www.drugbank.ca/drugs/DB00997	Inhibitor 8297
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17194596	Inhibitor 8297	2.67 µM [IC50]
A673 8 Target ID: CHEMBL614517 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27688190	Inhibitor 8297	200.0 nM [IC50]
HepG2 16 Target ID: CHEMBL395 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27669220	Inhibitor 8297	24.68 µM [IC50]
Human ovarian cancer cell line 8 Target ID: CHEMBL613895 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26694484	Inhibitor 8297	0.074 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Locally advanced or unresectable soft tissue sarcoma 8 Sources: https://clinicaltrials.gov/ct2/show/NCT02049905	Primary	Phase III 656	Unknown Approved Use Unknown
Kaposi’s sarcoma 13 Sources: https://clinicaltrials.gov/ct2/show/NCT02029430	Primary	Phase II 1132	Unknown Approved Use Unknown
Glioblastoma 65 Sources: https://clinicaltrials.gov/ct2/show/NCT02014844	Primary	Phase II 1132	Unknown Approved Use Unknown
Metastatic non-small cell lung cancer 13 Sources: https://clinicaltrials.gov/ct2/show/NCT02200757	Primary	Phase II 1132	Unknown Approved Use Unknown
Pancreatic ductal adenocarcinoma 14 Sources: https://clinicaltrials.gov/ct2/show/NCT01580397	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050718s045lbl.pdf	Primary	Approved 8429	DOXIL Approved Use Indicated for: Ovarian cancer After failure of platinum-based chemotherapy. AIDS-related Kaposi’s Sarcoma After failure of prior systemic chemotherapy or intolerance to such therapy. Multiple Myeloma Launch Date 1995
AIDS-related Kaposi’s sarcoma 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050718s045lbl.pdf	Primary	Approved 8429	DOXIL Approved Use Indicated for: Ovarian cancer After failure of platinum-based chemotherapy. AIDS-related Kaposi’s Sarcoma After failure of prior systemic chemotherapy or intolerance to such therapy. Multiple Myeloma Launch Date 1995
Multiple myeloma 159 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050718s045lbl.pdf	Primary	Approved 8429	DOXIL Approved Use Indicated for: Ovarian cancer After failure of platinum-based chemotherapy. AIDS-related Kaposi’s Sarcoma After failure of prior systemic chemotherapy or intolerance to such therapy. Multiple Myeloma Launch Date 1995

C_max

Value	Dose	Co-administered	Analyte	Population
2 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26115930	60 mg/m² 1 times / day steady-state, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:		DOXORUBICIN plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
7.4 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26115930	60 mg/m² 1 times / day steady-state, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:		DOXORUBICIN plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
34.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26115930	60 mg/m² 1 times / day steady-state, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: STEADY-STATE co-administered:		DOXORUBICIN plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
25% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050467s073lbl.pdf			DOXORUBICIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
150 mg/m2 1 times / day multiple, intravenous Overdose Dose: 150 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 150 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf	unhealthy, 17 years n = 1 Health Status: unhealthy Age Group: 17 years Sex: F Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf	Other AEs: Mucositis, Chills... Other AEs: Mucositis (severe, 1 patient) Chills (1 patient) Pyrexia (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf
300 mg/m2 single, intravenous Overdose Dose: 300 mg/m2 Route: intravenous Route: single Dose: 300 mg/m2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf	unhealthy, 58 years n = 1 Health Status: unhealthy Condition: acute lymphoblastic leukemia Age Group: 58 years Sex: M Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf	Other AEs: Sinus tachycardia, Neutropenia... Other AEs: Sinus tachycardia (1 patient) Neutropenia (grade 4, 1 patient) Thrombocytopenia (1 patient) Mucositis (severe, 1 patient) Sepsis (severe, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf
60 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 60 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 60 mg/m2, 1 times / 3 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf	Disc. AE: Tissue injury... Other AEs: Acute myeloid leukaemia, Myelodysplastic syndrome... AEs leading to discontinuation/dose reduction: Tissue injury (severe) Other AEs: Acute myeloid leukaemia Myelodysplastic syndrome Myelosuppression (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf
300 mg/m2 1 times / 3 weeks multiple, intravenous (total) Dose: 300 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 300 mg/m2, 1 times / 3 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf	Other AEs: Cardiomyopathy... Other AEs: Cardiomyopathy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050467s078,050629s030lbl.pdf
450 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 450 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 450 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/25312684 Page: p.574	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/25312684 Page: p.574	DLT: Neutropenia, Febrile neutropenia... Disc. AE: Anemia, Neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 50%) Febrile neutropenia (grade 3, 50%) AEs leading to discontinuation/dose reduction: Anemia (grade 3, 50%) Neutropenia (grade 3, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/25312684 Page: p.574
350 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 350 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 350 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/25312684 Page: p.574	unhealthy, ADULT n = 18 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/25312684 Page: p.574	DLT: Dehydration, Neutropenia... Disc. AE: Septic shock, Anemia... Dose limiting toxicities: Dehydration (5.6%) Neutropenia (5.6%) Sepsis (5.6%) AEs leading to discontinuation/dose reduction: Septic shock (grade 5, 5.6%) Anemia (grade 3, 5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/25312684 Page: p.574

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537 AKR1C3 13 NDUFS2 8 NDUFS3 8 NDUFS7 8 NQO1 8 XDH 8 MRP1 107 MRP2 205 BCRP 561 SLC22A16 8 MRP5 40 OATP1A2 62 OATP1B1 406 OATP1B3 350	CYP1A1 108 CYP1A2 701 CYP1B1 51 CYP2B2 15 CYP2E1 128 CYP2J3 8 CYP2C11 14 CYP2B1 26 CYP2C23 10

Drug as perpetrator

Target	Modality	Activity
CYP2B1 41	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	no
CYP2C23 10	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	no
CYP2C11 15	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	weak
CYP1A1 218	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	yes
CYP1A2 1692	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	yes
CYP1B1 67	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	yes
CYP2B2 16	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	yes
CYP2E1 970	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	yes
CYP2J3 8	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1537189108000864 Page: -	yes

Drug as victim

Target	Modality	Activity	Metabolite
SLC22A16 8	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006291X05011873 Page: -	yes [Km 5.2 uM]
AKR1C3 13	substrate 3367 Sources: https://www.pharmgkb.org/literature/8369411 Page: -	yes
BCRP 561	substrate 3367 Sources: https://www.pharmgkb.org/pathway/PA165292177 Page: -	yes
MRP1 107	substrate 3367 Sources: https://www.pharmgkb.org/pathway/PA165292177 Page: -	yes
MRP2 205	substrate 3367 Sources: https://www.pharmgkb.org/pathway/PA165292177 Page: -	yes
MRP5 40	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0378427401003915 Page: -	yes	GS-DOX 8
NDUFS2 8	substrate 3367 Sources: https://www.pharmgkb.org/pathway/PA165292177 Page: -	yes
NDUFS3 8	substrate 3367 Sources: https://www.pharmgkb.org/pathway/PA165292177 Page: -	yes
NDUFS7 8	substrate 3367 Sources: https://www.pharmgkb.org/pathway/PA165292177 Page: -	yes
NQO1 8	substrate 3367 Sources: https://www.pharmgkb.org/pathway/PA165292177 Page: -	yes
OATP1A2 62	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0378427401003915 Page: -	yes
OATP1B1 406	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0378427401003915 Page: -	yes
OATP1B3 350	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0378427401003915 Page: -	yes
P-gp 1537	substrate 3367 Sources: https://link.springer.com/article/10.1007/s12272-011-0411-x Page: -	yes
XDH 8	substrate 3367 Sources: https://www.pharmgkb.org/pathway/PA165292177 Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
AbovChem LLC	HY-16261A	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-16261A
BLD Pharm	BD630336	http://www.bldpharm.com/search/Search.html?keyword=BD630336
ChEBI	CHEBI:28748	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28748
Chem Scene	CS-0077171	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0077171
MedChem Express	HY-16261B	https://www.medchemexpress.com/search.html?q=HY-16261B&ft=&fa=&fp=
MolPort	MolPort-006-124-025	https://www.molport.com/shop/molecule-link/MolPort-006-124-025
ZINC	ZINC000003918087	http://zinc15.docking.org/substances/ZINC000003918087
eMolecules	50284280	https://orderbb.emolecules.com/search/#?query=50284280
eMolecules	36788175	https://www.emolecules.com/cgi-bin/more?vid=36788175
mcule	MCULE-8506890923	https://mcule.com/MCULE-8506890923/

PubMed

Title	Date	PubMed
Experimental animal models of adriamycin cardiotoxicity.	1979 May	110445
[Changes in left ventricular function during chemotherapy with doxorubicin].	1999 Jul	11045157
Nonmetastatic osteosarcoma of the extremity: results of a neoadjuvant chemotherapy protocol (IOR/OS-3) with high-dose methotrexate, intraarterial or intravenous cisplatin, doxorubicin, and salvage chemotherapy based on histologic tumor response.	1999 Nov-Dec	10774566
Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein inhibitor valspodar and mitotane or doxorubicin.	2000 Apr	10898547
Adriamycin-induced heart failure: mechanism and modulation.	2000 Apr	10888230
Doxorubicin-induced late cardiotoxicity: delayed impairment of Ca2+-handling mechanisms in the sarcoplasmic reticulum in the rat.	2000 Apr	10772060
Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2.	2000 Aug	11038041
The influence of coordinate overexpression of glutathione phase II detoxification gene products on drug resistance.	2000 Aug	10900222
The protective effect of glutathione administration on adriamycin-induced acute cardiac toxicity in rats.	2000 Aug	10887039
Fas-mediated apoptosis in adriamycin-induced cardiomyopathy in rats: In vivo study.	2000 Aug 1	10920071
Deregulated manganese superoxide dismutase expression and resistance to oxidative injury in p53-deficient cells.	2000 Aug 15	10969820
Cytokine gene expression in Adriamycin nephropathy: effects of antioxidant nuclear factor kappaB inhibitors in established disease.	2000 Dec	11124598
Progressive cardiac dysfunction in adriamycin-induced cardiomyopathy rats.	2000 Dec	11113713
High incidence of adriamycin cardiotoxicity in children even at low cumulative doses: role of radionuclide cardiac angiography.	2000 Dec	11101737
Proteasome-mediated degradation of the coactivator p300 impairs cardiac transcription.	2000 Dec	11073966
Doxorubicin and paclitaxel in advanced breast carcinoma: importance of prior adjuvant anthracycline therapy.	2000 Dec 1	11147586
Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.	2000 Dec 15	11135211
Liposomal doxorubicin (Caelyx) in advanced pretreated soft tissue sarcomas: a phase II study of the Italian Sarcoma Group (ISG).	2000 Jan-Feb	10769710
Manic episode in an ifosfamide-treated patient.	2000 Jan-Feb	10766557
Influence of Adriamycin and paraquat on antioxidant enzyme expression in primary rat hepatocytes.	2000 Jul	10959798
Doxorubicin-induced cardiomyopathy.	2000 Jul	10910374
Cardiac peroxynitrite formation and left ventricular dysfunction following doxorubicin treatment in mice.	2000 Jul	10871338
Oxidative stress interferes with cancer chemotherapy: inhibition of lymphoma cell apoptosis and phagocytosis.	2000 Jul 1	10891466
Effects of probucol on changes of antioxidant enzymes in adriamycin-induced cardiomyopathy in rats.	2000 Jun	10912462
Beta-blockade in adriamycin-induced cardiomyopathy.	2000 Jun	10908085
Evaluation of cardiac adrenergic neuronal damage in rats with doxorubicin-induced cardiomyopathy using iodine-131 MIBG autoradiography and PGP 9.5 immunohistochemistry.	2000 Jun	10901455
Cardiac sequelae of doxorubicin and paclitaxel as induction chemotherapy prior to high-dose chemotherapy and peripheral blood progenitor cell transplantation in women with high-risk primary or metastatic breast cancer.	2000 May	10828864
Lovastatin potentiates antitumor activity and attenuates cardiotoxicity of doxorubicin in three tumor models in mice.	2000 May	10815931
Expression of agrin, dystroglycan, and utrophin in normal renal tissue and in experimental glomerulopathies.	2000 May	10793086
Caffeine-potentiated radiochemotherapy and function-saving surgery for high-grade soft tissue sarcoma.	2000 May-Jun	10928167
Phase II study of pegylated liposomal doxorubicin: inactive in recurrent small-cell lung cancer. A Hellenic Cooperative Oncology Group Study.	2000 Nov	11142478
Detection of doxorubicin cardiotoxicity by using iodine-123 BMIPP early dynamic SPECT: quantitative evaluation of early abnormality of fatty acid metabolism with the Rutland method.	2000 Nov-Dec	11144469
Renal antioxidant enzymes and fibrosis-related markers in the rat adriamycin model.	2000 Oct	11014987
Progressive adriamycin nephropathy in mice: sequence of histologic and immunohistochemical events.	2000 Oct	11012915
Bilateral blindness and lumbosacral myelopathy associated with high-dose carmustine and cisplatin therapy.	2000 Sep	11020424
Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum.	2000 Sep	10985896
Prevention of doxorubicin (adriamycin)-induced cardiomyopathy by simultaneous administration of angiotensin-converting enzyme inhibitor assessed by acoustic densitometry.	2000 Sep	10975594
Human carbonyl reductase overexpression in the heart advances the development of doxorubicin-induced cardiotoxicity in transgenic mice.	2000 Sep 15	11016643
ACE inhibition preserves heparan sulfate proteoglycans in the glomerular basement membrane of rats with established adriamycin nephropathy.	2001	11053977
Mobilization of hematopoietic progenitor cells with a combination of docetaxel, adriamycin, 5-fluorouracil and filgrastim in breast cancer patients.	2001 Jan	11146579
Low-grade ovarian cancer in an adolescent patient.	2001 Jan	11136580
Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma in hamsters.	2001 Jan	11115548
Reversal of LRP-associated drug resistance in colon carcinoma SW-620 cells.	2001 Jan 1	11149411
Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation.	2001 Jan 1	11134193
Characterization of adriamycin-induced G2 arrest and its abrogation by caffeine in FL-amnion cells with or without p53.	2001 Jan 1	11120603
Nuclear factor kappaB-dependent mechanisms coordinate the synergistic effect of PMA and cytokines on the induction of superoxide dismutase 2.	2001 Jan 1	11115408
Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.	2001 Jan 12	11111016
Repression of cyclin B1 expression after treatment with adriamycin, but not cisplatin in human lung cancer A549 cells.	2001 Jan 26	11162602
Mycosis fungoides and pregnancy.	2001 Jan-Feb	11115598
Human mismatch repair and G*T mismatch binding by hMutSalpha in vitro is inhibited by adriamycin, actinomycin D, and nogalamycin.	2001 Mar 30	11134041

Patents

Sample Use Guides

In Vivo Use Guide

When used in combination with other chemotherapy drugs, the most commonly used dosage of doxorubicin is 40 to 60 mg/m2 IV every 21 to 28 days. Alternatively, 60 to 75 mg/m2 IV once every 21 days.

Route of Administration: Intravenous

In Vitro Use Guide

Alkalinization of extracellular pH by urease (2 U/ml) and urea (> or = 2 mM) was found to enhance the antitumor efficacy of doxorubicin (50 uM)

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:24:52 GMT 2023` Edited by `admin` on `Sat Dec 16 11:24:52 GMT 2023`
Record UNII	4IA03SIO30
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZOPTARELIN DOXORUBICIN ACETATE

Official Name

English

(6-D-LYSINE)HUMAN GONADOLIBERIN-1 (LHRH) AND DOXORUBICIN COVALENTLY LINKED TOGETHER WITH GLUTARIC ACID: 5-OXO-L-PROLYL-L-HISTIDYL-L-TRYPTOPHYL-L-SERYL-L-TYROSYL-N6-(5-(2-((2S,4S)-4-((3-AMINO-2,3,6-TRIDEOXY-.ALPHA.-L-LYXO-HEXOPYRANOSYL)OXY)-2,5,12-TRIHYDR

Systematic Name

English

ZEN-008

Code

English

AEZS-108

Code

English

LUTEINIZING HORMONE-RELEASING FACTOR (SWINE), 6-(N6-(5-(2-((2S,4S)-4-((3-AMINO-2,3,6-TRIDEOXY-.ALPHA.-L-LYXO-HEXOPYRANOSYL)OXY)-1,2,3,4,6,11-HEXAHYDRO-2,5,12-TRIHYDROXY-7-METHOXY-6,11-DIOXO-2-NAPHTHACENYL)-2-OXOETHOXY)-1,5-DIOXOPENTYL)-D-LYSINE)-, ACETATE

Systematic Name

English

ZOPTARELIN DOXORUBICIN ACETATE [USAN]

Common Name

English

AN-152

Code

English

D-81858

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

304410