U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C23H31Cl2NO3
Molecular Weight 440.4039
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTRAMUSTINE

SMILES

C[C@@]12CC[C@]3([H])c4ccc(cc4CC[C@@]3([H])[C@]2([H])CC[C@]1([H])O)OC(=O)N(CCCl)CCCl

InChI

InChIKey=FRPJXPJMRWBBIH-RBRWEJTLSA-N
InChI=1S/C23H31Cl2NO3/c1-23-9-8-18-17-5-3-16(29-22(28)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)27/h3,5,14,18-21,27H,2,4,6-13H2,1H3/t18-,19-,20+,21+,23+/m1/s1

HIDE SMILES / InChI

Molecular Formula C23H31Cl2NO3
Molecular Weight 440.4039
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018045s023lbl.pdf

Estramustine is an antineoplastic agent indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a combination of estradiol with nitrogen mustard. In vivo, the nitrogen-mustard moiety becomes active and participates in alkylation of DNA or other cellular components. This causes DNA damage in rapidly dividing cancerous cells leading to cell death and ideally, tumor shrinkage. Also, due to the drugs estrogen component, it can bind more selectively to active estrogen receptors. Used for the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Emcyt

Approved Use

EMCYT Capsules are indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.

Launch Date

694137600000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
362 ng/mL
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.88 μg × h/mL
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
972 ng × h/mL
280 mg 3 times / day multiple, oral
dose: 280 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ESTRAMUSTINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.6 h
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
50%
ESTRAMUSTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3000 mg/m2 1 times / week multiple, intravenous
Highest studied dose
dose: 3000 mg/m2 1 times / week
route: intravenous
experiment_type: multiple
dose_type: Highest studied dose
co-adm with
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/11844837
    unhealthy, 66
    population: unhealthy
    age: 66
    sex: M
    food_status:
    n:
    data_source:
    https://pubmed.ncbi.nlm.nih.gov/11844837
    DLT: Malaise and fatigue, Hypotension...
    Dose limiting toxicities:
    Malaise and fatigue (grade 3, 75%)
    Hypotension (grade 3, 25%)

    data_source:
    https://pubmed.ncbi.nlm.nih.gov/11844837
    2500 mg/m2 1 times / week multiple, intravenous
    MTD
    dose: 2500 mg/m2 1 times / week
    route: intravenous
    experiment_type: multiple
    dose_type: MTD
    co-adm with
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/11844837
      unhealthy, 66
      population: unhealthy
      age: 66
      sex: M
      food_status:
      n:
      data_source:
      https://pubmed.ncbi.nlm.nih.gov/11844837
      DLT: Malaise and fatigue...
      Dose limiting toxicities:
      Malaise and fatigue (grade 3, 40%)

      data_source:
      https://pubmed.ncbi.nlm.nih.gov/11844837
      AEs

      AEs

      AESignificanceDosePopulation
      Malaise and fatigue grade 3,40%
      DLT
      2500 mg/m2 1 times / week multiple, intravenous
      MTD
      dose: 2500 mg/m2 1 times / week
      route: intravenous
      experiment_type: multiple
      dose_type: MTD
      co-adm with
        data_source:
        https://pubmed.ncbi.nlm.nih.gov/11844837
        unhealthy, 66
        population:
        age:
        sex:
        food_status:
        n:
        data_source:
        https://pubmed.ncbi.nlm.nih.gov/11844837
        Hypotension grade 3,25%
        DLT
        3000 mg/m2 1 times / week multiple, intravenous
        Highest studied dose
        dose: 3000 mg/m2 1 times / week
        route: intravenous
        experiment_type: multiple
        dose_type: Highest studied dose
        co-adm with
          data_source:
          https://pubmed.ncbi.nlm.nih.gov/11844837
          unhealthy, 66
          population:
          age:
          sex:
          food_status:
          n:
          data_source:
          https://pubmed.ncbi.nlm.nih.gov/11844837
          Malaise and fatigue grade 3,75%
          DLT
          3000 mg/m2 1 times / week multiple, intravenous
          Highest studied dose
          dose: 3000 mg/m2 1 times / week
          route: intravenous
          experiment_type: multiple
          dose_type: Highest studied dose
          co-adm with
            data_source:
            https://pubmed.ncbi.nlm.nih.gov/11844837
            unhealthy, 66
            population:
            age:
            sex:
            food_status:
            n:
            data_source:
            https://pubmed.ncbi.nlm.nih.gov/11844837
            Overview

            Overview

            CYP3A4CYP2C9CYP2D6hERG

            OverviewOther

            Other InhibitorOther SubstrateOther Inducer

            Drug as perpetrator​

            Drug as perpetrator​

            PubMed

            PubMed

            TitleDatePubMed
            Estramustine plus a taxane for advanced prostate cancer: the new standard therapy?
            2002
            Phase I trial of oral estramustine and 3-hr infusional paclitaxel for the treatment of hormone refractory prostate cancer.
            2002
            [Second cancer after starting treatment for prostate cancer].
            2002 Aug
            Ondansetron but not granisetron affect cell volume regulation and potassium ion transport of glioma cells treated with estramustine phosphate.
            2002 Aug
            Chemotherapy for androgen-independent prostate cancer.
            2002 Aug
            Editorial: the coming revolution in the treatment of prostate cancer patients.
            2002 Aug
            Hypertriglyceridemia and pancreatitis associated with estramustine phosphate.
            2002 Aug
            [Therapy for hormone-refractory prostate cancer].
            2002 Dec
            [Chemotherapy for prostate cancers].
            2002 Dec
            Fatal respiratory failure associated with treatment of prostate cancer using docetaxel and estramustine.
            2002 Dec
            An active regimen of weekly paclitaxel and estramustine in metastatic androgen-independent prostate cancer.
            2002 Dec
            Editorial: States and state transitions are all that really matter.
            2002 Dec
            Combination chemotherapy with paclitaxel, estramustine and carboplatin for hormone refractory prostate cancer.
            2002 Dec
            EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.
            2002 Feb
            Mechanism of action of antitumor drugs that interact with microtubules and tubulin.
            2002 Jan
            The antimicrotubule drug estramustine but not irradiation induces apoptosis in malignant glioma involving AKT and caspase pathways.
            2002 Jan
            The role of chemotherapy in advanced prostate cancer.
            2002 Jun
            Docetaxel in the integrated management of prostate cancer. Current applications and future promise.
            2002 Jun
            Effects of docetaxel on pain due to metastatic androgen-independent prostate cancer.
            2002 Jun
            Acute estramustine-induced hypocalcemia unmasking severe vitamin D deficiency.
            2002 Jun 1
            High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.
            2002 Jun 5
            A phase II Hoosier Oncology Group study of vinorelbine and estramustine phosphate in hormone-refractory prostate cancer.
            2002 Mar
            Estramustine phosphate enhances the effects of hyperthermia and induces the small heat shock protein HSP27 in the human prostate carcinoma cell line PC-3.
            2002 May
            Estramustine phosphate combined with orchidectomy as first-line therapy in patients with prostate carcinoma. Effect of age on survival.
            2002 May 15
            [Hormonal chemotherapy for hormone-refractory prostate cancer].
            2002 Nov
            Pattern of somatic androgen receptor gene mutations in patients with hormone-refractory prostate cancer.
            2002 Nov
            Penile metastasis of prostatic adenocarcinoma.
            2002 Oct
            Drug resistance in prostate cancer cell lines is influenced by androgen dependence and p53 status.
            2002 Oct
            Combined anti-microtubule therapy: a phase II study of weekly docetaxel plus estramustine in patients with metastatic breast cancer.
            2002 Oct
            Chemotherapy for prostate cancer.
            2002 Sep
            Weekly epirubicin in patients with hormone-resistant prostate cancer.
            2002 Sep 23
            Role of chemotherapy in hormone-refractory prostate cancer. Old issues, recent advances and new perspectives.
            2003
            [Prostatic cancer in the young adult].
            2003 Apr
            Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locallyadvanced prostate cancer.
            2003 Apr
            A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma.
            2003 Feb 1
            Estimating survival benefit in castrate metastatic prostate cancer: decision making in proceeding to a definitive phase III trial.
            2003 Jan
            A phase I study of paclitaxel, estramustine phosphate and vinorelbine (Pacl-E-Vin) in advanced malignancies: triple tubulin targeting.
            2003 Jan
            Bisphosphonate therapy for hormone refractory prostate cancer with bone metastasis.
            2003 Jan
            Docetaxel (taxotere) in the treatment of prostate cancer.
            2003 Jun
            The combination of estramustine and mitoxantrone in hormone-refractory prostate cancer: a phase II feasibility study conducted by the Hellenic Cooperative Oncology Group.
            2003 Jun
            Dose escalation study of intravenous estramustine phosphate in combination with Paclitaxel and Carboplatin in patients with advanced prostate cancer.
            2003 Jun
            Current strategies in the management of hormone refractory prostate cancer.
            2003 Jun
            [Malignant priapism as a sign of a recurrent prostate cancer. Differential diagnosis of induratio penis plastica].
            2003 Jun
            Chemotherapy of prostate cancer: present and future.
            2003 Jun
            Randomized, multicenter, phase II trial of two multicomponent regimens in androgen-independent prostate cancer.
            2003 Mar 1
            Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts.
            2003 May
            Physician attitudes toward cytotoxic chemotherapy use in patients with advanced prostate carcinoma.
            2003 May 1
            Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells.
            2003 May 16
            Neoadjuvant therapy before radical prostatectomy in high-risk localized prostate cancer: defining appropriate endpoints.
            2003 May-Jun
            High-risk localized prostate cancer: primary surgery and adjuvant therapy.
            2003 May-Jun
            Patents

            Sample Use Guides

            In Vivo Use Guide
            The recommended daily dose is 14 mg per kg of body weight (ie, one 140 mg capsule for each 10 kg or 22 lb of body weight), given in 3 or 4 divided doses. Most patients in studies in the United States have been treated at a dosage range of 10 to 16 mg per kg per day.
            Route of Administration: Oral
            Estramustine inhibited human endothelial cell proliferation with an IC50 of 4.5 uM and was active at 10-33% of the maximum tolerated dose (MTD) from clinical schedules
            Substance Class Chemical
            Created
            by admin
            on Sat Jun 26 13:15:53 UTC 2021
            Edited
            by admin
            on Sat Jun 26 13:15:53 UTC 2021
            Record UNII
            35LT29625A
            Record Status Validated (UNII)
            Record Version
            • Download
            Name Type Language
            ESTRAMUSTINE
            INN   MI   USAN   VANDF   WHO-DD  
            USAN   INN  
            Official Name English
            RO-22-2296/000
            Code English
            RO 22-2296/000
            Code English
            NSC-89201
            Code English
            ESTRAMUSTINE [INN]
            Common Name English
            RO-222296000
            Code English
            RO-22-2296000
            Code English
            ESTRAMUSTINE [WHO-DD]
            Common Name English
            ESTRA-1,3,5(10)-TRIENE-3,17-DIOL, 3-(BIS(2-CHLOROETHYL)CARBAMATE), (17B)-
            Common Name English
            ESTRAMUSTINE [USAN]
            Common Name English
            ESTRAMUSTINE [MI]
            Common Name English
            ESTRAMUSTINE [VANDF]
            Common Name English
            ESTRADIOL 3-(BIS(2-CHLOROETHYL)CARBAMATE)
            Common Name English
            Classification Tree Code System Code
            NDF-RT N0000007246
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            WHO-ATC L01XX11
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            NDF-RT N0000175558
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            LIVERTOX 373
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            NDF-RT N0000007246
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            NCI_THESAURUS C697
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            NCI_THESAURUS C25974
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            NDF-RT N0000007659
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            WHO-VATC QL01XX11
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            NDF-RT N0000000236
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            Code System Code Type Description
            EVMPD
            SUB07246MIG
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            MESH
            D004961
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            MERCK INDEX
            M5031
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY Merck Index
            WIKIPEDIA
            ESTRAMUSTINE
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            RXCUI
            4089
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY RxNorm
            DRUG BANK
            DB01196
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            EPA CompTox
            2998-57-4
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            NCI_THESAURUS
            C479
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            ChEMBL
            CHEMBL1575
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            PUBCHEM
            259331
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            FDA UNII
            35LT29625A
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            ECHA (EC/EINECS)
            221-076-3
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            CAS
            2998-57-4
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            DRUG CENTRAL
            1065
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            INN
            2877
            Created by admin on Sat Jun 26 13:15:54 UTC 2021 , Edited by admin on Sat Jun 26 13:15:54 UTC 2021
            PRIMARY
            Related Record Type Details
            METABOLITE -> PARENT
            PRODRUG -> METABOLITE ACTIVE
            Related Record Type Details
            ACTIVE MOIETY