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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H29NO11.ClH
Molecular Weight 579.98
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DOXORUBICIN HYDROCHLORIDE

SMILES

Cl.[H][C@@]1(C[C@H](N)[C@H](O)[C@H](C)O1)O[C@H]2C[C@@](O)(CC3=C(O)C4=C(C(=O)C5=C(OC)C=CC=C5C4=O)C(O)=C23)C(=O)CO

InChI

InChIKey=MWWSFMDVAYGXBV-RUELKSSGSA-N
InChI=1S/C27H29NO11.ClH/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34;/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3;1H/t10-,13-,15-,17-,22+,27-;/m0./s1

HIDE SMILES / InChI

Description

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 TargetPharmacologyConditionPotency
2.67 µM [IC50]
2.67 µM [IC50]
200.0 nM [IC50]
24.68 µM [IC50]
0.074 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
DOXIL
Primary
DOXIL

Cmax

ValueDoseCo-administeredAnalytePopulation
2 μM
60 mg/m² 1 times / day steady-state, intravenous
DOXORUBICIN plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
7.4 μM × h
60 mg/m² 1 times / day steady-state, intravenous
DOXORUBICIN plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
34.8 h
60 mg/m² 1 times / day steady-state, intravenous
DOXORUBICIN plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
25%
DOXORUBICIN plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

PubMed

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)