RANIMUSTINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H18ClN3O7
Molecular Weight	327.719
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O

InChI

InChIKey=AHHFEZNOXOZZQA-ZEBDFXRSSA-N

InChI=1S/C10H18ClN3O7/c1-20-9-8(17)7(16)6(15)5(21-9)4-12-10(18)14(13-19)3-2-11/h5-9,15-17H,2-4H2,1H3,(H,12,18)/t5-,6-,7+,8-,9+/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.genome.jp/dbget-bin/www_bget?D01760
Curator's Comment: Description was created based on several sources, including DOI: 10.1007/978-3-319-13278-5 Retrieved from Molecular Therapies of Cancer By Georg F. Weber, p.26 and http://www.ncbi.nlm.nih.gov/pubmed/2405779

Ranimustine (tradename Cymerin; also known as MCNU) is a nitrosourea alkylating agent approved in Japan for the treatment of chronic myelogenous leukemia and polycythemia vera. It has never been filed for FDA evaluation in the United States, where it is not marketed.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
cell growth 21 Target ID: GO:0016049 Sources: http://www.ncbi.nlm.nih.gov/pubmed/9625826	Inhibitor 8504
DNA synthesis involved in DNA replication 11 Target ID: GO:0090592 Sources: http://www.genome.jp/dbget-bin/www_bget?D01760	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic myelogenous leukemia 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2817908	Primary		Approved 8583	Cymerin Approved Use Polycythemia vera treatment medicines Launch Date 2014
Polycythemia vera 18 Sources: http://drugs-about.com/drugs-c/cymerin.html	Primary		Approved 8583	Cymerin Approved Use Polycythemia vera treatment medicines Launch Date 2014

C_max

Value	Dose	Co-administered	Analyte	Population
9.1 μg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/4/430920_4219402D1028_4_100_1F.pdf#page=26	150 mg single, intravenous dose: 150 mg route of administration: Intravenous experiment type: SINGLE co-administered:		RANIMUSTINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
41 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/4/430920_4219402D1028_4_100_1F.pdf#page=26	150 mg single, intravenous dose: 150 mg route of administration: Intravenous experiment type: SINGLE co-administered:		RANIMUSTINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
40% EXPERIMENT https://www.info.pmda.go.jp/go/interview/4/430920_4219402D1028_4_100_1F.pdf#page=27			RANIMUSTINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
600 mg/kg single, intravenous Highest studied dose Dose: 600 mg/kg Route: intravenous Route: single Dose: 600 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/2574565/	unhealthy, CHILD Health Status: unhealthy Age Group: CHILD Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2574565/	Other AEs: Interstitial pneumoniti... Other AEs: Interstitial pneumoniti Sources: https://pubmed.ncbi.nlm.nih.gov/2574565/

AEs

AE	Significance	Dose	Population
Interstitial pneumoniti		600 mg/kg single, intravenous Highest studied dose Dose: 600 mg/kg Route: intravenous Route: single Dose: 600 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/2574565/	unhealthy, CHILD Health Status: unhealthy Age Group: CHILD Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2574565/

PubMed

Title	Date	PubMed
A nonradiation-containing, intermediate-dose methotrexate regimen for elderly patients with primary central nervous system lymphoma.	2010-11	20967518
[Plasmacytoma of chest wall].	2010-09	20845698
Aortic thrombus in a patient with myeloproliferative thrombocytosis, successfully treated by pharmaceutical therapy: a case report.	2010-07-21	20663173
Treatment of atypical central neurocytoma in a child with high dose chemotherapy and autologous stem cell rescue.	2010-05	19924515
A pilot case-control study on the alveolar bone density measurement in risk assessment for bisphosphonate-related osteonecrosis of the jaw.	2010-05	19705049
Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group.	2010-02	19597416
Successful treatment with autologous peripheral blood stem cell transplantation for acquired immunodeficiency syndrome (AIDS)-related malignant lymphoma.	2009-11	20009441
Changes in serum tryptophan catabolism as an indicator of disease activity in adult T-cell leukemia/lymphoma.	2009-08	19544139
Interferon-beta, MCNU, and conventional radiotherapy for pediatric patients with brainstem glioma.	2009-07	19260101
[Long-term remission of non-Hodgkin lymphoma secondary to the treatment for essential thrombocythemia].	2009-03	19352088
Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.	2009	19204798
Autologous stem cell transplantation using MEAM regimen for relapsed AIDS-related lymphoma patients who received highly active anti-retroviral therapy: a report of three cases.	2009	19145056
Chemotherapeutic choice of ranimustine or nimustine on the basis of regional polyamine levels in rat brain.	2008-03	18560626
VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801.	2007-12-01	17968021
Genetically heterogeneous glioblastoma recurring with disappearance of 1p/19q losses: case report.	2007-07	17621007
Evaluation of intratumoral administration of tumor necrosis factor-alpha in patients with malignant glioma.	2007-01-02	17195453
[Four cases of therapy-related leukemia in multiple myeloma].	2007-01	17220686
Multiple granulocytic sarcomas in essential thrombocythemia.	2006-12	17189221
[Development of acute type, CD 8 positive adult T-cell leukemia in a carrier of hepatitis B virus--possible therapeutic effect of lamivudine combined with chemotherapy].	2006-05	16685173
Successful chemotherapy for congenital malignant gliomas: a report of two cases.	2006	16714866
[Autologous hematopoietic stem cell transplantation for aggressive B-cell non-Hodgkin's lymphoma].	2005-12	16352929
Efficacy and feasibility of procarbazine, ranimustine and vincristine chemotherapy, and the role of surgical resection in anaplastic oligodendroglioma.	2005-11-24	16302731
Supratentorial primitive neuroectodermal tumor in an aged patient--case report--.	2005-10	16247240
Irinotecan therapy in a 12-year-old girl with recurrent brain stem glioma and without functional polymorphisms in UGT1A1 activity: case report.	2005-09	16187025
[A case of high grade astrocytoma arising in the hand area of precentral gyrus].	2005-06	16026048
[Trial of front-line intensive chemotherapy followed by peripheral blood stem cell transplantation in high-intermediate and high risk non-Hodgkin's lymphoma patients].	2005-05	16444968
[Effective combination therapy of bortezomib and dexamethasone for two patients with refractory multiple myeloma].	2005-04	16444959
[Focal segmental glomerulosclerosis in a patient with polycythemia vera].	2005	16296413
[Multiple myeloma of the IgD-lambda type invading CNS].	2004-10	15553049
[CD56-positive peripheral T-cell lymphoma primarily presenting with tonsillar swelling].	2004-10	15553048
[Granulocyte-colony stimulating factor-producing myeloma with clinical manifestations mimicking chronic neutrophilic leukemia].	2004-03	15103937
[Pneumocystis carinii pneumonia complicating brain tumor].	2004-02	15031973
Phase III study of ranimustine, cyclophosphamide, vincristine, melphalan, and prednisolone (MCNU-COP/MP) versus modified COP/MP in multiple myeloma: a Japan clinical oncology group study, JCOG 9301.	2004-02	15005346
Infrainguinal bypass surgery for chronic arterial occlusive disease associated with essential thrombocythemia: report of a case.	2004	15221564
Recombinant mutant human tumor necrosis factor-alpha (TNF-SAM2) immunotherapy with ranimustine chemotherapy and concurrent radiation therapy for malignant astrocytomas.	2003-12-12	14666736
Cardiac lymphoma successfully treated with high dose chemotherapy followed by autologous haematopoietic stem cell transplantation.	2003-12	14688007
Successful high-dose chemotherapy for widespread neuroaxis dissemination of an optico-hypothalamic juvenile pilocytic astrocytoma in an infant: a case report.	2003-05	12777080
Combination chemotherapy of ranimustine, doxorubicine, and dexamethasone for relapsing multiple myeloma--a pilot study.	2003	17682310
[Therapeutic effectiveness of ranimustine chemotherapy for essential thrombocythemia in the elderly].	2002-11	12518414
Megakaryoblastic transformation of polycythemia vera with hypercalcemia.	2002-11	12454709
[A case of primary malignant lymphoma of the pararectal space].	2002-09	12402484
[A case of chronic thromboembolic pulmonary hypertension based on essential thrombocythemia].	2002-07	12382421
[A case of multiple myeloma with infiltration into skeletal muscle after injections of a granulocyte-colony stimulating-factor].	2002-07	12187809
Superior efficacy of MMCP regimen compared with VMCP and MMPP regimens in the treatment of multiple myeloma.	2002-04	11993789
Leukemic transformation with trisomy 8 in essential thrombocythemia: a report of four cases.	2002-02	12061320
Reversible restrictive cardiomyopathy due to light-chain deposition disease.	2002-02	11838655
Malignant melanoma of the anorectum: report of four cases.	2002	12107786
Interferon-alpha therapy following autologous peripheral blood stem cell transplantation for adult T cell leukemia/lymphoma.	2002	12053149
[Perioperative management for radical esophagectomy in a patient with polycythemia vera].	2001-12	11797364
[Syndrome of inappropriate secretion of antidiuretic hormone and neurotoxicity induced by vincristine and alkylating agents during chemotherapy for malignant lymphoma of thyroid gland].	1998-04	9571977

Patents

Sample Use Guides

In Vivo Use Guide

oral administration of 50mg (one tablet)/body/day every 4-6 days was considered as one course, and this was repeated at 6-8-week intervals if possible

Route of Administration: Oral

In Vitro Use Guide

The SD10 (10% survival dose) of the cells to Ranimustine ranged from 4.3 uM (C6-2 cells) to 151.7 uM (T98G cells).

Name

Type

Language

RANIMUSTINE

Official Name

English

CYMERIN

Preferred Name

English

RANIMUSTINE [MART.]

Common Name

English

Ranimustine [WHO-DD]

Common Name

English

METHYL 6-(3-(2-CHLOROETHYL)-3-NITROSOUREIDO)-6-DEOXY-.ALPHA.-D-GLUCOPYRANOSIDE

Common Name

English

RANIMUSTINE [JAN]

Common Name

English

RANIMUSTINE [MI]

Common Name

English

NSC-270516

Code

English

ranimustine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C699