MECHLORETHAMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C5H11Cl2N
Molecular Weight	156.054
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(CCCl)CCCl

InChI

InChIKey=HAWPXGHAZFHHAD-UHFFFAOYSA-N

InChI=1S/C5H11Cl2N/c1-8(4-2-6)5-3-7/h2-5H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/19480393

Mechlorethamine also known as mustine, brand name MUSTARGEN administered intravenously is the prototype anticancer chemotherapeutic drug, is indicated for the palliative treatment of Hodgkin's disease (Stages III and IV), lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia, polycythemia vera, mycosis fungoides, and bronchogenic carcinoma. In 2013 was approved orphan drug Valchlor (mechlorethamine) gel for the topical treatment of stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma (CTCL) in patients who have received prior skin-directed therapy. Mechlorethamine belongs to the group of nitrogen mustard alkylating agents. Alkylating agents work by three different mechanisms: attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations all of which achieve the same end result - disruption of DNA function and cell death.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19480393	Crosslinking Agent 81

Conditions

Condition	Modality	Highest Phase	Product
Hodgkin's disease (Stages III and IV) 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8429	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date 1949
Lymphosarcoma 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8429	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date 1949
Chronic lymphocytic leukemia 59 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8429	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date 1949
Chronic myelocytic leukemia 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8429	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date 1949
Mycosis fungoides 30 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf	Palliative	Approved 8429	MUSTARGEN Approved Use VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy (1). Launch Date 1949

C_max

Value	Dose	Co-administered	Analyte	Population
1.72 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11129502	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		MECHLORETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
3.17 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11129502	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		MECHLORETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.16 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11129502	0.2 mg/kg single, oral dose: 0.2 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		MECHLORETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 14-80 n = 26 Health Status: unhealthy Condition: Reticulum cell sarcoma Age Group: 14-80 Sex: M+F Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	Disc. AE: Thrombocytopenia, Hemorrhage... AEs leading to discontinuation/dose reduction: Thrombocytopenia (severe, 3.8%) Hemorrhage (3.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 32-81 n = 18 Health Status: unhealthy Condition: Lymphosarcoma Age Group: 32-81 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	Disc. AE: Pancytopenia... AEs leading to discontinuation/dose reduction: Pancytopenia (5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
0.02 % 1 times / day multiple, topical Recommended Dose: 0.02 %, 1 times / day Route: topical Route: multiple Dose: 0.02 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517	unhealthy, 44 n = 20 Health Status: unhealthy Condition: Psoriasis Age Group: 44 Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517	Disc. AE: Contact dermatitis... AEs leading to discontinuation/dose reduction: Contact dermatitis (75%) Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517
0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	Disc. AE: Eye injury, Dermatitis... AEs leading to discontinuation/dose reduction: Eye injury Dermatitis Cancer of skin (excl melanoma) Disorder fetal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
0.4 mg/kg single, intravenous (total) Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Hodgkin's disease\| lymphosarcoma\|chronic myelocytic leukemia\| chronic lymphocytic leukemia\| polycythemia vera\| mycosis fungoides\|bronchogenic carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2	Disc. AE: Amyloidosis... AEs leading to discontinuation/dose reduction: Amyloidosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2

AEs

AE	Significance	Dose	Population
Hemorrhage	3.8% Disc. AE	0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 14-80 n = 26 Health Status: unhealthy Condition: Reticulum cell sarcoma Age Group: 14-80 Sex: M+F Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
Thrombocytopenia	severe, 3.8% Disc. AE	0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 14-80 n = 26 Health Status: unhealthy Condition: Reticulum cell sarcoma Age Group: 14-80 Sex: M+F Population Size: 26 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
Pancytopenia	5.6% Disc. AE	0.4 mg/kg single, intravenous Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413	unhealthy, 32-81 n = 18 Health Status: unhealthy Condition: Lymphosarcoma Age Group: 32-81 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/4569376 Page: p.413
Contact dermatitis	75% Disc. AE	0.02 % 1 times / day multiple, topical Recommended Dose: 0.02 %, 1 times / day Route: topical Route: multiple Dose: 0.02 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517	unhealthy, 44 n = 20 Health Status: unhealthy Condition: Psoriasis Age Group: 44 Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2933055 Page: p.517
Cancer of skin (excl melanoma)	Disc. AE	0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
Dermatitis	Disc. AE	0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
Disorder fetal	Disc. AE	0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
Eye injury	Disc. AE	0.016 % 1 times / day multiple, topical Recommended Dose: 0.016 %, 1 times / day Route: topical Route: multiple Dose: 0.016 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202317lbl.pdf Page: p.1
Amyloidosis	Disc. AE	0.4 mg/kg single, intravenous (total) Recommended Dose: 0.4 mg/kg Route: intravenous Route: single Dose: 0.4 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2	unhealthy Health Status: unhealthy Condition: Hodgkin's disease\| lymphosarcoma\|chronic myelocytic leukemia\| chronic lymphocytic leukemia\| polycythemia vera\| mycosis fungoides\|bronchogenic carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/06695slr031_mustargen_lbl.pdf Page: p.2

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28925	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28925
ZINC	ZINC000002539484	http://zinc15.docking.org/substances/ZINC000002539484
eMolecules	729204	https://www.emolecules.com/cgi-bin/more?vid=729204

PubMed

Title	Date	PubMed
A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy.	1992 Oct	1329697
Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) for advanced-stage Hodgkin's disease: CALGB 8856.	2001	11458812
Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2.	2001 Aug	11763419
Advanced Hodgkin disease with large mediastinal involvement can be treated with eight cycles of chemotherapy alone after a major response to six cycles of chemotherapy: a study of 82 patients from the Groupes d'Etudes des Lymphomes de l'Adulte H89 trial.	2001 Aug 1	11505388
Hematological malignancies and pregnancy: a final report of 84 children who received chemotherapy in utero.	2001 Dec	11779294
The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange.	2001 Dec	11751423
Chromatin structure at the 3'-boundary of the human beta-globin locus control region hypersensitive site-2.	2001 Dec	11606254
DNA interstrand crosslink formation by mechlorethamine at a cytosine-cytosine mismatch pair: kinetics and sequence dependence.	2001 Feb 15	11368336
[Gene protective effect of the short-chain derivative of Vitamin E under the action of alkylating compounds].	2001 Jan-Feb	11589037
The serum levels of eosinophil cationic protein (ECP) are related to the infiltration of eosinophils in the tumours of patients with Hodgkin's disease.	2001 Jul	11699410
Follicular mycosis fungoides: a case report and review of the literature.	2001 Jul	11401680
Prophylactic efficacy of amifostine and its analogues against sulphur mustard toxicity.	2001 Jun 21	11516517
Phenotypes of Drosophila homologs of human XPF and XPG to chemically-induced DNA modifications.	2001 May 9	11336992
[Successful chemotherapy of cancer. Remission of Hodgkin's disease. IV].	2001 May-Jun	11692542
Adult lymphoblastic lymphoma in Taiwan: an analysis of treatment results of 26 patients.	2001 Nov	11757723
Hypoxia-selective antitumor agents. 16. Nitroarylmethyl quaternary salts as bioreductive prodrugs of the alkylating agent mechlorethamine.	2001 Oct 11	11585455
ESMO minimum clinical recommendations for diagnosis, treatment and follow-up of Hodgkin's disease.	2001 Sep	11697828
[Z-form of intraphage DNA].	2002	12534267
[Psoriasis of the scalp].	2002 Dec	12536184
Postpneumonectomy-like syndrome after chemoradiation therapy for lymphoma.	2002 Dec	12453864
Serum levels of soluble CD30 improve International Prognostic Score in predicting the outcome of advanced Hodgkin's lymphoma.	2002 Dec	12453859
An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.	2002 Dec 15	12467067
Subdiaphragmatic Hodgkin's disease: the University of Florida experience.	2002 Jan 1	11777634
[Advanced oxidation protein products in pregnancy].	2002 Jul	12373919
Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer.	2002 Jul 1	12097302
Topical treatment with povidone iodine reduces nitrogen mustard-induced skin collagenolytic activity.	2002 Mar	11914782
Covalent binding of nitrogen mustards to the cysteine-34 residue in human serum albumin.	2002 Mar	11914777
Involvement of phosphatidylinositol-3-kinase in membrane ruffling induced by P-glycoprotein substrates in multidrug-resistant carcinoma cells.	2002 Mar 1	11911848
European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease.	2002 Mar 15	11920535
Radiotherapy alone for lymphocyte-predominant Hodgkin's disease.	2002 Sep-Oct	12416895
MOPP chemotherapy for treatment of resistant lymphoma in dogs: a retrospective study of 117 cases (1989-2000).	2002 Sep-Oct	12322709
Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas.	2003 Apr	12852367
Differential diagnosis of Fanconi anemia by nitrogen mustard and diepoxybutane.	2003 Apr	12707724
[Hodgkin's disease manifesting as paraneoplastic limbic encephalitis].	2003 Apr	12706783
The protective and therapeutic effects of zinc chloride and desferrioxamine on skin exposed to nitrogen mustard.	2003 Aug	12943035
Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience.	2003 Feb	12588222
Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial.	2003 Feb 15	12586796
Advanced Hodgkin's disease: ABVD is better, yet is not good enough!	2003 Feb 15	12586791
Topical nitrogen mustard ointment with occlusion for Langerhans' cell histiocytosis of the scalp.	2003 Jan	12745855
[Cutaneous T-cell lymphoma following renal transplantation].	2003 Jan	12605158
Improved survival in HIV-related Hodgkin's lymphoma since the introduction of highly active antiretroviral therapy.	2003 Jan 3	12478072
Quantitative determination of the hydrolysis products of nitrogen mustards in human urine by liquid chromatography-electrospray ionization tandem mass spectrometry.	2003 Jan-Feb	12587675
Revascularization for acute coronary occlusion in a young woman following radiation.	2003 Jul	14507117
Injury induced by chemical warfare agents: characterization and treatment of ocular tissues exposed to nitrogen mustard.	2003 Jul	12824239
Radiation therapy in the treatment of Hodgkin's disease--do you see what I see?	2003 Jul 2	12837820
Early and intermediate stage Hodgkin's lymphoma--report from the Swedish National Care Programme.	2003 Mar	12605661
Topical mechlorethamine restores autoimmune-arrested follicular activity in mice with an alopecia areata-like disease by targeting infiltrated lymphocytes.	2003 Mar	12603852
Synthesis and in vivo biodisposition of [14C]-quaternary ammonium-melphalan conjugate, a potential cartilage-targeted alkylating drug.	2003 Mar-Apr	12643763
Management of mycosis fungoides: Part 2. Treatment.	2003 Oct	14606365
[Hematologic tumors].	2003 Oct	14584273

Patents

Sample Use Guides

In Vivo Use Guide

Intravenous Administration: the dosage of MUSTARGEN (MECHLORETHAMINE HCl ) varies with the clinical situation, the therapeutic response and the magnitude of hematologic depression. A total dose of 0.4 mg/kg of body weight for each course usually is given either as a single dose or in divided doses of 0.1 to 0.2 mg/kg per day. Intracavitary Administration: The usual dose of nitrogen mustard for intracavitary injection is 0.4 mg/kg of body weight, though 0.2 mg/kg (or 10 to 20 mg) has been used by the intrapericardial route.5,11-13 The solution is prepared, as previously described for intravenous injection, by adding 10 mL of Sterile Water for Injection or 10 mL of Sodium Chloride Injection to the vial containing 10 mg of mechlorethamine hydrochloride. (Amounts of diluent of 50 to 100 mL of normal saline have also been used.4,5) The position of the patient should be changed every 5 to 10 minutes for an hour after injection to obtain more uniform distribution of the drug throughout the serous cavity. The remaining fluid may be removed from the pleural or peritoneal cavity by paracentesis 24 to 36 hours later. The patient should be followed carefully by clinical and x-ray examination to detect reaccumulation of fluid.

Route of Administration: Other

In Vitro Use Guide

Unknown

Name

Type

Language

MECHLORETHAMINE

Common Name

English

2,2'-DICHLORO-N-METHYLDIETHYLAMINE

Common Name

English

MECHLORETHAMINE [MI]

Common Name

English

chlormethine [INN]

Common Name

English

MECHLORETHAMINE [HSDB]

Common Name

English

METHYL-.BETA.,.BETA.-DICHLORODIETHYLAMINE

Common Name

English

DIETHYLAMINE, 2,2'-DICHLORO-N-METHYL-

Systematic Name

English

NITROGEN MUSTARD (HN 2)

Common Name

English

NSC-128663

Code

English

CHLORETHAZINE

Common Name

English

CHLORMETHINE

Official Name

English

ETHANAMINE, 2-CHLORO-N-(2-CHLOROETHYL)-N-METHYL-

Systematic Name

English

NSC-757087

Code

English

NITROGEN MUSTARD

Common Name

English

MECHLORETHAMINE [VANDF]

Common Name

English

NITROGEN MUSTARD [IARC]

Common Name

English

Chlormethine [WHO-DD]

Common Name

English

NSC-10107

Code

English

Classification Tree Code System Code

LIVERTOX

NBK548509