melphalan Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	1678	148-82-3

Description:

Molecule

Description

Molfile Inchi Smiles Synonyms: melphalan hydrochloride melphalan alkeran levofalan levofolan levopholan melfalan phenylalanine mustard sarcoclorin melphalan HCl

An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen. Molecular weight: 305.20 Formula: C13H18Cl2N2O2 CLOGP: -0.21 LIPINSKI: 0 HAC: 4 HDO: 2 TPSA: 66.56 ALOGS: -2.93 ROTB: 8 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.10 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	12 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.33 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	71 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.48 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	7 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.14 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	1 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Jan. 17, 1964	FDA	GLAXOSMITHKLINE

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Acute graft versus host disease	510.29	17.15	148	20230	3882	46661802
Graft versus host disease	450.53	17.15	151	20227	6437	46659247
Mucosal inflammation	440.23	17.15	250	20128	38726	46626958
Plasma cell myeloma	346.73	17.15	225	20153	44253	46621431
Myelodysplastic syndrome	345.10	17.15	158	20220	15553	46650131
Venoocclusive liver disease	341.20	17.15	110	20268	4141	46661543
Adenovirus infection	327.71	17.15	97	20281	2733	46662951
Febrile neutropenia	319.98	17.15	291	20087	94336	46571348
Thrombotic microangiopathy	300.40	17.15	119	20259	8187	46657497
Acute graft versus host disease in skin	284.30	17.15	88	20290	2894	46662790
Cytomegalovirus infection	270.47	17.15	140	20238	18004	46647680
Chronic graft versus host disease	241.28	17.15	76	20302	2649	46663035
Neutropenia	229.73	17.15	297	20081	142907	46522777
Acute graft versus host disease in intestine	191.45	17.15	57	20321	1638	46664046
Acute myeloid leukaemia	180.04	17.15	102	20276	15676	46650008
Thrombocytopenia	177.54	17.15	246	20132	126335	46539349
Pancytopenia	172.89	17.15	199	20179	84859	46580825
Osteonecrosis	168.64	17.15	117	20261	25627	46640057
Graft versus host disease in skin	164.71	17.15	55	20323	2312	46663372
Venoocclusive disease	162.60	17.15	52	20326	1904	46663780
Cytomegalovirus infection reactivation	151.16	17.15	46	20332	1426	46664258
BK virus infection	139.71	17.15	51	20327	2798	46662886
Graft versus host disease in gastrointestinal tract	137.62	17.15	49	20329	2501	46663183
Epstein-Barr virus infection	132.68	17.15	63	20315	6721	46658963
Sepsis	124.24	17.15	217	20161	135797	46529887
Stem cell transplant	122.74	17.15	41	20337	1725	46663959
Product use in unapproved indication	121.30	17.15	172	20206	90101	46575583
Viraemia	117.76	17.15	35	20343	999	46664685
Haemophagocytic lymphohistiocytosis	109.05	17.15	59	20319	8283	46657401
Cystitis haemorrhagic	104.86	17.15	44	20334	3503	46662181
Headache	103.40	17.15	40	20338	478312	46187372
Human herpesvirus 6 infection	102.54	17.15	39	20339	2400	46663284
Post transplant lymphoproliferative disorder	101.32	17.15	44	20334	3812	46661872
Cytomegalovirus viraemia	101.29	17.15	46	20332	4432	46661252
Malignant transformation	100.05	17.15	24	20354	291	46665393
Plasma cell myeloma recurrent	95.86	17.15	37	20341	2370	46663314
Mucosal disorder	93.05	17.15	34	20344	1870	46663814
Bone marrow failure	91.80	17.15	87	20291	29582	46636102
Retinal pigment epitheliopathy	91.32	17.15	21	20357	209	46665475
Posterior reversible encephalopathy syndrome	90.28	17.15	65	20313	15076	46650608
Drug hypersensitivity	86.39	17.15	5	20373	243820	46421864
Prothrombin level increased	84.90	17.15	20	20358	223	46665461
Pyrexia	83.86	17.15	337	20041	348465	46317219
Chronic graft versus host disease in skin	83.85	17.15	24	20354	598	46665086
Engraftment syndrome	81.73	17.15	20	20358	265	46665419
Epstein-Barr viraemia	79.83	17.15	24	20354	713	46664971
Second primary malignancy	78.97	17.15	44	20334	6540	46659144
Arthralgia	76.21	17.15	32	20346	364571	46301113
Varicella zoster virus infection	75.80	17.15	31	20347	2312	46663372
Vitreous haemorrhage	75.77	17.15	29	20349	1815	46663869
Osteonecrosis of jaw	72.33	17.15	82	20296	34320	46631364
Premature menopause	72.07	17.15	22	20356	689	46664995
Acute graft versus host disease in liver	70.01	17.15	21	20357	619	46665065
Acute myeloid leukaemia recurrent	68.48	17.15	25	20353	1371	46664313
Iris atrophy	67.51	17.15	13	20365	48	46665636
Engraft failure	67.01	17.15	18	20360	352	46665332
Stomatitis	66.22	17.15	112	20266	68185	46597499
Malaise	66.16	17.15	31	20347	331201	46334483
Chorioretinal atrophy	65.54	17.15	13	20365	58	46665626
Encephalitis viral	64.71	17.15	25	20353	1605	46664079
Infection	63.14	17.15	163	20215	133429	46532255
Viral haemorrhagic cystitis	62.27	17.15	19	20359	594	46665090
Eye excision	62.17	17.15	12	20366	45	46665639
Pneumonia fungal	61.65	17.15	32	20346	4128	46661556
Off label use	61.54	17.15	327	20051	379514	46286170
Acute lymphocytic leukaemia	61.18	17.15	28	20350	2745	46662939
Cytomegalovirus test positive	60.73	17.15	28	20350	2792	46662892
Aplasia	60.26	17.15	30	20348	3546	46662138
Progressive multifocal leukoencephalopathy	59.30	17.15	45	20333	11301	46654383
Neuropathy peripheral	57.16	17.15	124	20254	90769	46574915
Fall	55.39	17.15	38	20340	329059	46336625
Fatigue	54.95	17.15	115	20263	608582	46057102
Multiple organ dysfunction syndrome	54.42	17.15	88	20290	51622	46614062
Joint swelling	54.23	17.15	5	20373	166068	46499616
Dizziness	53.80	17.15	42	20336	340372	46325312
Pain	53.05	17.15	79	20299	476869	46188815
Bone debridement	52.70	17.15	15	20363	366	46665318
Tooth extraction	52.33	17.15	40	20338	10153	46655531
Choroidal infarction	51.78	17.15	11	20367	73	46665611
Refractory cytopenia with multilineage dysplasia	51.26	17.15	12	20366	130	46665554
Chronic myelomonocytic leukaemia	50.48	17.15	14	20364	310	46665374
Cytomegalovirus chorioretinitis	48.96	17.15	20	20358	1487	46664197
Bronchopulmonary aspergillosis	48.89	17.15	34	20344	7462	46658222
Bacterial sepsis	48.77	17.15	26	20352	3541	46662143
Plasmacytoma	48.41	17.15	23	20355	2454	46663230
Eyelid rash	48.23	17.15	10	20368	58	46665626
Septic shock	47.17	17.15	88	20290	57805	46607879
Enterococcal infection	46.29	17.15	32	20346	6955	46658729
Hypogonadism female	45.81	17.15	8	20370	14	46665670
Hepatitis B reactivation	45.48	17.15	19	20359	1495	46664189
Nasal abscess	45.00	17.15	11	20367	145	46665539
Pain in extremity	44.67	17.15	29	20349	258651	46407033
Enterococcal sepsis	44.27	17.15	18	20360	1322	46664362
Gastrointestinal fungal infection	43.60	17.15	12	20366	258	46665426
Abdominal discomfort	43.36	17.15	7	20371	151158	46514526
Epstein-Barr virus associated lymphoproliferative disorder	42.56	17.15	18	20360	1461	46664223
Pericardial effusion	42.39	17.15	54	20324	25489	46640195
Nasopharyngitis	42.28	17.15	8	20370	153990	46511694
Renal failure	42.18	17.15	127	20251	113467	46552217
Extraocular muscle disorder	41.78	17.15	10	20368	120	46665564
Morganella infection	41.15	17.15	13	20365	457	46665227
JC virus infection	40.54	17.15	18	20360	1644	46664040
Feeling abnormal	40.20	17.15	4	20374	125056	46540628
Product dose omission issue	39.89	17.15	12	20366	168508	46497176
Febrile bone marrow aplasia	39.85	17.15	29	20349	6833	46658851
Idiopathic pneumonia syndrome	39.80	17.15	12	20366	360	46665324
Anxiety	39.52	17.15	15	20363	181942	46483742
Mucocutaneous ulceration	39.35	17.15	10	20368	156	46665528
Plasma cell leukaemia	39.33	17.15	16	20362	1177	46664507
Bone disorder	39.15	17.15	46	20332	19987	46645697
Cardiac failure	38.19	17.15	98	20280	79850	46585834
Dyspnoea	38.09	17.15	108	20270	515440	46150244
Chest pain	37.53	17.15	15	20363	176309	46489375
Sinus polyp	37.24	17.15	11	20367	307	46665377
Eyelid oedema	37.14	17.15	33	20345	10324	46655360
Respiratory syncytial virus infection	36.47	17.15	24	20354	4811	46660873
Peripheral swelling	36.09	17.15	12	20366	158059	46507625
Heterochromia iridis	34.54	17.15	6	20372	10	46665674
Endocarditis bacterial	34.26	17.15	12	20366	583	46665101
Tonsillar haemorrhage	32.77	17.15	9	20369	192	46665492
Growth failure	32.67	17.15	10	20368	316	46665368
Enophthalmos	32.64	17.15	6	20372	16	46665668
Neuralgic amyotrophy	32.11	17.15	6	20372	18	46665666
Nausea	31.64	17.15	174	20204	687280	45978404
Follicular thyroid cancer	31.59	17.15	7	20371	58	46665626
Retinoblastoma	31.47	17.15	8	20370	125	46665559
Gastrointestinal mucosal disorder	31.44	17.15	12	20366	745	46664939
Alopecia	31.15	17.15	16	20362	162398	46503286
Pruritus	31.10	17.15	36	20342	242316	46423368
Depression	30.82	17.15	18	20360	170086	46495598
Sequestrectomy	30.80	17.15	13	20365	1050	46664634
Epstein-Barr virus infection reactivation	30.27	17.15	9	20369	257	46665427
Herpes zoster	30.16	17.15	81	20297	67791	46597893
Pulmonary haemorrhage	30.08	17.15	24	20354	6481	46659203
Blood pressure increased	30.00	17.15	9	20369	126657	46539027
Chronic graft versus host disease in intestine	29.97	17.15	7	20371	75	46665609
Condition aggravated	29.75	17.15	38	20340	245014	46420670
Cardiac failure acute	29.49	17.15	26	20352	8052	46657632
Escherichia bacteraemia	29.20	17.15	17	20361	2744	46662940
Eyelid ptosis	28.97	17.15	23	20355	6165	46659519
Haematotoxicity	28.74	17.15	24	20354	6909	46658775
Transplant failure	28.73	17.15	13	20365	1241	46664443
Overdose	28.62	17.15	5	20373	101974	46563710
Urticaria	28.61	17.15	8	20370	117884	46547800
Drug interaction	28.47	17.15	28	20350	203066	46462618
Bacteraemia	28.44	17.15	33	20345	14146	46651538
Cardiomyopathy	28.29	17.15	35	20343	16038	46649646
Plastic surgery	28.05	17.15	7	20371	101	46665583
Disease progression	27.45	17.15	95	20283	91205	46574479
Osteolysis	27.41	17.15	16	20362	2596	46663088
Mucosal erosion	27.38	17.15	13	20365	1385	46664299
Bronchospasm	27.32	17.15	34	20344	15673	46650011
Peritonitis viral	27.26	17.15	6	20372	48	46665636
Loss of consciousness	26.92	17.15	7	20371	108231	46557453
Asthma	26.78	17.15	4	20374	91538	46574146
Ovarian failure	26.78	17.15	12	20366	1120	46664564
Polyneuropathy	26.60	17.15	29	20349	11615	46654069
Myelosuppression	26.54	17.15	24	20354	7679	46658005
Cytopenia	26.37	17.15	24	20354	7744	46657940
Adenoviral haemorrhagic cystitis	26.20	17.15	7	20371	134	46665550
Pneumonia cytomegaloviral	25.99	17.15	14	20364	1946	46663738
Hyperhidrosis	25.91	17.15	4	20374	89304	46576380
Blood stem cell transplant failure	25.54	17.15	7	20371	148	46665536
Complications of bone marrow transplant	25.45	17.15	9	20369	450	46665234
Leukopenia	24.96	17.15	76	20302	68267	46597417
Encephalopathy	24.81	17.15	49	20329	33540	46632144
Hepatitis B	24.67	17.15	17	20361	3676	46662008
Disease recurrence	24.47	17.15	35	20343	18436	46647248
Gait disturbance	24.08	17.15	17	20361	145246	46520438
Actinomycosis	24.05	17.15	11	20367	1077	46664607
Jaw operation	23.96	17.15	10	20368	785	46664899
Infection reactivation	23.94	17.15	10	20368	787	46664897
Osteomyelitis	23.40	17.15	38	20340	22345	46643339
Iris neovascularisation	23.06	17.15	5	20373	37	46665647
Fungaemia	23.04	17.15	13	20365	1978	46663706
Myocardial infarction	22.96	17.15	7	20371	97521	46568163
Purulent discharge	22.72	17.15	18	20360	4812	46660872
Acute respiratory distress syndrome	22.63	17.15	37	20341	21885	46643799
Urethritis	22.58	17.15	7	20371	231	46665453
Acute promyelocytic leukaemia	22.54	17.15	10	20368	911	46664773
Bone sequestrum	22.33	17.15	12	20366	1661	46664023
Gastrointestinal toxicity	22.24	17.15	17	20361	4314	46661370
Chest discomfort	22.14	17.15	6	20372	90263	46575421
Arthropathy	21.99	17.15	5	20373	84695	46580989
Refractory cancer	21.90	17.15	5	20373	48	46665636
Lymphopenia	21.77	17.15	30	20348	15263	46650421
Graft versus host disease in liver	21.72	17.15	8	20370	450	46665234
Leukaemia	21.61	17.15	15	20363	3280	46662404
Acute kidney injury	21.46	17.15	176	20202	235679	46430005
Cerebral vasoconstriction	21.44	17.15	10	20368	1023	46664661
Acinetobacter infection	21.25	17.15	11	20367	1411	46664273
Contusion	21.11	17.15	6	20372	87481	46578203
Platelet count decreased	21.04	17.15	93	20285	99931	46565753
Infusion related reaction	20.89	17.15	9	20369	101199	46564485
Culture stool positive	20.63	17.15	7	20371	309	46665375
Oral disorder	20.57	17.15	21	20357	7801	46657883
Chronic myeloid leukaemia	20.51	17.15	13	20365	2445	46663239
Weight decreased	20.49	17.15	38	20340	210811	46454873
Pseudomonal sepsis	20.31	17.15	12	20366	1990	46663694
Graft versus host disease in lung	20.25	17.15	7	20371	327	46665357
Pityriasis	20.21	17.15	3	20375	0	46665684
Klebsiella bacteraemia	20.21	17.15	10	20368	1166	46664518
Oral fungal infection	20.14	17.15	13	20365	2521	46663163
Chronic graft versus host disease in liver	20.13	17.15	6	20372	173	46665511
Gastrooesophageal reflux disease	20.10	17.15	4	20374	74340	46591344
Hepatic vein occlusion	19.86	17.15	5	20373	75	46665609
Toxicity to various agents	19.79	17.15	159	20219	211607	46454077
Intraductal proliferative breast lesion	19.74	17.15	13	20365	2609	46663075
Osteitis	19.73	17.15	14	20364	3171	46662513
Myalgia	19.63	17.15	15	20363	123073	46542611
Encephalitis	19.59	17.15	20	20358	7428	46658256
Insomnia	19.56	17.15	26	20352	164898	46500786
Aspartate aminotransferase increased	19.55	17.15	77	20301	78623	46587061
Schistocytosis	19.32	17.15	4	20374	23	46665661
Memory impairment	19.23	17.15	5	20373	77332	46588352
Arthritis	19.22	17.15	5	20373	77311	46588373
Leukaemia recurrent	19.20	17.15	10	20368	1299	46664385
Bronchiolitis obliterans syndrome	19.11	17.15	5	20373	88	46665596
Respiratory failure	19.08	17.15	87	20291	94729	46570955
Aspergillus infection	19.04	17.15	19	20359	6871	46658813
JC virus CSF test positive	19.04	17.15	4	20374	25	46665659
Type III immune complex mediated reaction	18.88	17.15	6	20372	215	46665469
Hypogammaglobulinaemia	18.85	17.15	17	20361	5421	46660263
Palpitations	18.83	17.15	9	20369	95250	46570434
Hypersensitivity	18.55	17.15	23	20355	150298	46515386
Refractory anaemia with an excess of blasts	18.44	17.15	7	20371	428	46665256
Heart rate increased	18.28	17.15	5	20373	74786	46590898
Gastroenteritis rotavirus	18.23	17.15	5	20373	106	46665578
Abdominal pain upper	18.17	17.15	22	20356	145283	46520401
IIIrd nerve disorder	18.13	17.15	3	20375	3	46665681
Hospitalisation	18.02	17.15	3	20375	63382	46602302
Cerebrovascular accident	17.86	17.15	11	20367	101028	46564656
Endothelial dysfunction	17.68	17.15	5	20373	119	46665565
Choroidal dystrophy	17.67	17.15	3	20375	4	46665680
Uterine atrophy	17.56	17.15	4	20374	38	46665646
Retinal depigmentation	17.44	17.15	6	20372	276	46665408
Acetabulum fracture	17.30	17.15	6	20372	283	46665401

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Acute graft versus host disease	585.58	16.35	211	25193	5653	29921421
Venoocclusive liver disease	564.49	16.35	212	25192	6401	29920673
Myelodysplastic syndrome	480.41	16.35	259	25145	18519	29908555
Mucosal inflammation	443.05	16.35	292	25112	30202	29896872
Plasma cell myeloma	390.03	16.35	339	25065	53123	29873951
Acute myeloid leukaemia	372.31	16.35	216	25188	17790	29909284
Graft versus host disease	331.37	16.35	165	25239	9985	29917089
Febrile neutropenia	328.24	16.35	427	24977	106266	29820808
Acute graft versus host disease in skin	287.14	16.35	117	25287	4399	29922675
Chronic graft versus host disease	242.47	16.35	101	25303	4018	29923056
Venoocclusive disease	199.19	16.35	77	25327	2513	29924561
Malignant transformation	171.40	16.35	50	25354	663	29926411
Cytomegalovirus infection	170.04	16.35	149	25255	23525	29903549
Adenovirus infection	168.29	16.35	79	25325	4189	29922885
Graft versus host disease in gastrointestinal tract	166.42	16.35	71	25333	2998	29924076
Acute graft versus host disease in intestine	165.59	16.35	66	25338	2339	29924735
Human herpesvirus 6 infection	160.55	16.35	61	25343	1897	29925177
Thrombotic microangiopathy	158.77	16.35	96	25308	8514	29918560
Second primary malignancy	133.24	16.35	77	25327	6279	29920795
Osteonecrosis	133.13	16.35	110	25294	16025	29911049
Chorioretinal atrophy	131.54	16.35	27	25377	63	29927011
Graft versus host disease in skin	129.72	16.35	61	25343	3246	29923828
Product use in unapproved indication	126.23	16.35	225	25179	73468	29853606
Off label use	123.11	16.35	476	24928	248814	29678260
Neutropenia	119.60	16.35	306	25098	128234	29798840
Multiple organ dysfunction syndrome	112.78	16.35	197	25207	63290	29863784
Epstein-Barr virus infection	108.98	16.35	69	25335	6637	29920437
Stem cell transplant	107.99	16.35	47	25357	2084	29924990
Mucosal disorder	104.40	16.35	42	25362	1525	29925549
Cytomegalovirus viraemia	103.35	16.35	63	25341	5666	29921408
Drug interaction	102.80	16.35	22	25382	199546	29727528
Plasma cell myeloma recurrent	101.12	16.35	52	25352	3362	29923712
Pancytopenia	96.77	16.35	219	25185	84833	29842241
Tooth extraction	92.19	16.35	55	25349	4756	29922318
Engraftment syndrome	90.75	16.35	32	25372	801	29926273
Bronchopulmonary aspergillosis	89.53	16.35	78	25326	12206	29914868
Sepsis	87.66	16.35	298	25106	146097	29780977
Retinal pigment epitheliopathy	86.33	16.35	23	25381	213	29926861
Bone disorder	82.15	16.35	58	25346	6683	29920391
Basal cell carcinoma	80.68	16.35	83	25321	15985	29911089
Choroidal dystrophy	78.05	16.35	16	25388	37	29927037
Haemophagocytic lymphohistiocytosis	77.11	16.35	65	25339	9726	29917348
Epstein-Barr viraemia	76.77	16.35	29	25375	887	29926187
Thrombocytopenia	75.97	16.35	272	25132	136772	29790302
Headache	75.74	16.35	30	25374	182276	29744798
Aspergillus infection	74.72	16.35	65	25339	10149	29916925
Acute graft versus host disease in liver	74.62	16.35	31	25373	1223	29925851
Refractory anaemia with an excess of blasts	74.56	16.35	23	25381	373	29926701
Pyrexia	72.81	16.35	462	24942	294027	29633047
Choroidal infarction	68.91	16.35	16	25388	78	29926996
Fatigue	68.56	16.35	104	25300	320569	29606505
Chronic graft versus host disease in skin	68.43	16.35	25	25379	695	29926379
Stomatitis	67.85	16.35	117	25287	37162	29889912
Dizziness	66.07	16.35	42	25362	194867	29732207
Cystitis haemorrhagic	64.94	16.35	44	25360	4743	29922331
Blood stem cell transplant failure	64.73	16.35	21	25383	404	29926670
Engraft failure	63.42	16.35	21	25383	432	29926642
Progressive multifocal leukoencephalopathy	63.21	16.35	56	25348	8957	29918117
Extraocular muscle disorder	61.84	16.35	17	25387	179	29926895
BK virus infection	61.33	16.35	41	25363	4323	29922751
Neuropathy peripheral	60.51	16.35	163	25241	70312	29856762
Parainfluenzae virus infection	60.23	16.35	31	25373	2007	29925067
Vitreous haemorrhage	59.22	16.35	31	25373	2079	29924995
Malaise	57.91	16.35	35	25369	166927	29760147
Aplasia	56.91	16.35	38	25366	3999	29923075
Bacterial sepsis	56.84	16.35	41	25363	4885	29922189
Product dose omission issue	56.45	16.35	6	25398	91625	29835449
Arthralgia	53.69	16.35	24	25380	135767	29791307
Diffuse large B-cell lymphoma	53.56	16.35	48	25356	7793	29919281
Herpes zoster	51.91	16.35	92	25312	29851	29897223
Apoptosis	51.27	16.35	15	25389	201	29926873
Posterior reversible encephalopathy syndrome	51.15	16.35	49	25355	8658	29918416
Fall	50.44	16.35	48	25356	181824	29745250
Dyspnoea	49.85	16.35	133	25271	333162	29593912
Staphylococcal sepsis	49.40	16.35	50	25354	9441	29917633
Transplant failure	48.95	16.35	29	25375	2475	29924599
Haematotoxicity	48.66	16.35	41	25363	6129	29920945
Overdose	48.34	16.35	7	25397	84330	29842744
Post transplant lymphoproliferative disorder	47.59	16.35	38	25366	5268	29921806
Epstein-Barr virus associated lymphoproliferative disorder	47.39	16.35	25	25379	1703	29925371
Prothrombin level increased	47.02	16.35	13	25391	140	29926934
Septic shock	46.65	16.35	139	25265	63468	29863606
Weight decreased	46.50	16.35	36	25368	150885	29776189
Chest pain	46.16	16.35	21	25383	117606	29809468
Bone debridement	45.28	16.35	15	25389	309	29926765
Eyelid oedema	44.97	16.35	36	25368	5009	29922065
Debridement	43.97	16.35	20	25384	985	29926089
Cytopenia	43.90	16.35	44	25360	8212	29918862
Sequestrectomy	43.69	16.35	15	25389	346	29926728
Cytomegalovirus test positive	43.57	16.35	31	25373	3614	29923460
Pneumonia cytomegaloviral	43.51	16.35	28	25376	2768	29924306
Bone sequestrum	43.21	16.35	18	25386	715	29926359
Gastrointestinal mucosal disorder	43.13	16.35	15	25389	360	29926714
Transformation to acute myeloid leukaemia	41.95	16.35	17	25387	629	29926445
Acute lymphocytic leukaemia	41.11	16.35	28	25376	3044	29924030
Bacterial infection	40.97	16.35	52	25352	12558	29914516
Juvenile melanoma benign	40.64	16.35	10	25394	65	29927009
Death	40.61	16.35	161	25243	357122	29569952
Neutropenic sepsis	40.19	16.35	49	25355	11360	29915714
Cerebral toxoplasmosis	39.53	16.35	21	25383	1451	29925623
Depression	38.97	16.35	14	25390	90423	29836651
Systemic candida	38.91	16.35	26	25378	2738	29924336
Myocardial infarction	38.64	16.35	30	25374	125595	29801479
Ameloblastoma	38.40	16.35	10	25394	84	29926990
Cerebrovascular accident	37.57	16.35	12	25392	83465	29843609
Bone marrow failure	37.54	16.35	80	25324	29705	29897369
Hepatitis B	37.24	16.35	35	25369	6037	29921037
Hepatic infection fungal	37.15	16.35	11	25393	154	29926920
Rhabdomyolysis	37.08	16.35	5	25399	63575	29863499
Eyelid rash	37.03	16.35	8	25396	26	29927048
Squamous cell carcinoma of skin	36.91	16.35	42	25362	9053	29918021
Blood pressure increased	36.81	16.35	8	25396	71920	29855154
Meningomyelitis herpes	36.15	16.35	8	25396	30	29927044
Acute respiratory distress syndrome	35.49	16.35	68	25336	23404	29903670
Peripheral swelling	35.15	16.35	5	25399	61069	29866005
Iris atrophy	34.73	16.35	9	25395	74	29927000
Metastases to retroperitoneum	34.13	16.35	11	25393	207	29926867
Anxiety	33.79	16.35	17	25387	89854	29837220
Chorioretinal disorder	33.35	16.35	7	25397	19	29927055
Refractory cytopenia with multilineage dysplasia	33.26	16.35	10	25394	148	29926926
Bone sarcoma	33.16	16.35	9	25395	90	29926984
JC virus infection	33.09	16.35	20	25384	1770	29925304
Myalgia	32.80	16.35	12	25392	76655	29850419
Asthenia	32.47	16.35	89	25315	221201	29705873
Drug hypersensitivity	32.38	16.35	9	25395	68510	29858564
Osteomyelitis	31.99	16.35	50	25354	14631	29912443
Hyperhidrosis	31.35	16.35	9	25395	67081	29859993
Somnolence	31.18	16.35	22	25382	96741	29830333
Osteosarcoma	31.14	16.35	10	25394	186	29926888
Ureaplasma infection	31.09	16.35	10	25394	187	29926887
Human herpesvirus 8 infection	31.06	16.35	14	25390	675	29926399
Hepatic vein occlusion	30.40	16.35	9	25395	126	29926948
Metastases to muscle	30.32	16.35	10	25394	203	29926871
Feeling abnormal	29.68	16.35	6	25398	56750	29870324
Meningoencephalitis herpetic	29.43	16.35	14	25390	764	29926310
Idiopathic pneumonia syndrome	29.23	16.35	10	25394	228	29926846
Lymphopenia	28.92	16.35	45	25359	13118	29913956
Human herpesvirus 6 encephalitis	28.89	16.35	9	25395	151	29926923
Coronary artery disease	28.77	16.35	4	25400	49708	29877366
Short stature	28.52	16.35	7	25397	45	29927029
Polyneuropathy	28.21	16.35	42	25362	11781	29915293
Carbamoyl phosphate synthetase deficiency	28.14	16.35	6	25398	18	29927056
Urticaria	28.08	16.35	6	25398	54600	29872474
Viral haemorrhagic cystitis	28.08	16.35	14	25390	847	29926227
Acute lymphocytic leukaemia recurrent	28.06	16.35	21	25383	2646	29924428
Plasmacytoma	27.91	16.35	23	25381	3333	29923741
Neoplasm recurrence	27.34	16.35	18	25386	1849	29925225
Autoimmune neutropenia	27.27	16.35	10	25394	281	29926793
Expanded disability status scale score increased	26.91	16.35	9	25395	191	29926883
Bradycardia	26.80	16.35	11	25393	65515	29861559
Pruritus	26.45	16.35	37	25367	118167	29808907
Obliterative bronchiolitis	26.40	16.35	15	25389	1183	29925891
Pain	26.39	16.35	68	25336	172573	29754501
Adenocarcinoma of colon	26.21	16.35	22	25382	3270	29923804
Eye excision	26.06	16.35	6	25398	28	29927046
Autoimmune haemolytic anaemia	26.06	16.35	24	25380	4035	29923039
Respiratory syncytial virus infection	25.78	16.35	22	25382	3346	29923728
Inflammatory myofibroblastic tumour	25.69	16.35	8	25396	134	29926940
Metastases to spleen	25.67	16.35	10	25394	333	29926741
Nasopharyngitis	25.53	16.35	9	25395	58840	29868234
Staphylococcal bacteraemia	25.36	16.35	30	25374	6738	29920336
Chronic graft versus host disease in intestine	25.31	16.35	9	25395	231	29926843
Myelitis	25.00	16.35	12	25392	668	29926406
Bacteraemia	24.66	16.35	46	25358	15514	29911560
Premature ageing	24.63	16.35	7	25397	84	29926990
Purulent discharge	24.51	16.35	20	25384	2859	29924215
Klebsiella sepsis	23.81	16.35	16	25388	1701	29925373
Hypoglycaemia	23.52	16.35	7	25397	50974	29876100
Chest discomfort	23.38	16.35	5	25399	45475	29881599
Graft versus host disease in liver	23.31	16.35	13	25391	989	29926085
Cytogenetic abnormality	23.24	16.35	12	25392	782	29926292
Iris neovascularisation	23.21	16.35	5	25399	16	29927058
Gait disturbance	22.79	16.35	18	25386	74759	29852315
Blood glucose increased	22.58	16.35	12	25392	61518	29865556
Hospitalisation	22.52	16.35	5	25399	44314	29882760
Neurotoxicity	22.19	16.35	40	25364	13142	29913932
Blood creatine phosphokinase increased	22.18	16.35	5	25399	43843	29883231
Myositis	22.13	16.35	35	25369	10342	29916732
Papilloma	22.11	16.35	7	25397	124	29926950
Complications of bone marrow transplant	22.11	16.35	8	25396	216	29926858
Tooth impacted	22.10	16.35	6	25398	60	29927014
Metastases to bone marrow	21.86	16.35	10	25394	499	29926575
Pneumonia	21.81	16.35	401	25003	333905	29593169
Capillary leak syndrome	21.80	16.35	15	25389	1657	29925417
Mycobacterium kansasii infection	21.77	16.35	8	25396	226	29926848
Exophthalmos	21.67	16.35	10	25394	509	29926565
Heterochromia iridis	21.52	16.35	4	25400	4	29927070
Plasma cell leukaemia	21.52	16.35	12	25392	913	29926161
Cytomegalovirus infection reactivation	21.46	16.35	15	25389	1700	29925374
Pain in extremity	21.34	16.35	38	25366	110183	29816891
Gingival erythema	21.28	16.35	7	25397	141	29926933
Pulmonary alveolar haemorrhage	21.15	16.35	27	25377	6554	29920520
Balance disorder	20.97	16.35	3	25401	36490	29890584
Inflammatory pseudotumour	20.96	16.35	5	25399	28	29927046
Laryngeal cancer metastatic	20.74	16.35	6	25398	77	29926997
Vision blurred	20.69	16.35	5	25399	41811	29885263
Confusional state	20.67	16.35	53	25351	134781	29792293
Joint swelling	20.67	16.35	7	25397	46939	29880135
Retinoblastoma	20.66	16.35	5	25399	30	29927044
Activated partial thromboplastin time shortened	20.63	16.35	9	25395	401	29926673
Jaw operation	20.38	16.35	8	25396	272	29926802
Osteolysis	20.35	16.35	14	25390	1546	29925528
Therapy partial responder	20.23	16.35	20	25384	3671	29923403
Insomnia	20.10	16.35	30	25374	93306	29833768
Chronic obstructive pulmonary disease	20.10	16.35	7	25397	46119	29880955
Infection	20.07	16.35	124	25280	77950	29849124
B precursor type acute leukaemia	20.07	16.35	6	25398	87	29926987
Hyperkalaemia	19.98	16.35	16	25388	65994	29861080
Genotoxicity	19.88	16.35	5	25399	36	29927038
Autoimmune pancytopenia	19.82	16.35	6	25398	91	29926983
B-cell lymphoma recurrent	19.64	16.35	10	25394	633	29926441
Hyperbilirubinaemia	19.63	16.35	44	25360	16898	29910176
Agitation	19.18	16.35	11	25393	54062	29873012
Pulmonary haemorrhage	19.10	16.35	31	25373	9361	29917713
Adenocarcinoma gastric	19.09	16.35	12	25392	1139	29925935
Toxic erythema of chemotherapy	18.99	16.35	5	25399	44	29927030
American trypanosomiasis	18.85	16.35	7	25397	204	29926870
Cytomegalovirus gastroenteritis	18.75	16.35	7	25397	207	29926867
Asthma	18.55	16.35	4	25400	36170	29890904
Amyloidosis	18.50	16.35	15	25389	2124	29924950
Musculoskeletal stiffness	18.33	16.35	4	25400	35877	29891197
Gastrointestinal injury	18.31	16.35	8	25396	358	29926716
Cardiac failure congestive	18.30	16.35	27	25377	84380	29842694
Febrile bone marrow aplasia	18.23	16.35	28	25376	8069	29919005
Retinal artery stenosis	18.22	16.35	3	25401	0	29927074
Disseminated varicella zoster virus infection	18.20	16.35	11	25393	973	29926101
Varicella zoster virus infection	18.02	16.35	12	25392	1256	29925818
International normalised ratio increased	17.98	16.35	9	25395	47730	29879344
Neutropenic colitis	17.96	16.35	15	25389	2215	29924859
Disseminated cryptococcosis	17.95	16.35	11	25393	998	29926076
Dental care	17.83	16.35	7	25397	238	29926836
Bone lesion	17.62	16.35	16	25388	2641	29924433
Adenosquamous cell lung cancer	17.49	16.35	4	25400	18	29927056
Tremor	17.44	16.35	23	25381	75340	29851734
Mantle cell lymphoma stage IV	17.44	16.35	5	25399	62	29927012
Herpes zoster meningoencephalitis	17.27	16.35	7	25397	259	29926815
Gastrointestinal toxicity	17.20	16.35	14	25390	1994	29925080
Candida sepsis	17.08	16.35	11	25393	1088	29925986
Condition aggravated	16.96	16.35	60	25344	137806	29789268
Bronchospasm	16.93	16.35	31	25373	10307	29916767
Spirochaetal infection	16.83	16.35	4	25400	22	29927052
Medulloblastoma recurrent	16.76	16.35	5	25399	72	29927002
Pneumonia fungal	16.69	16.35	22	25382	5511	29921563
Disease recurrence	16.65	16.35	37	25367	14124	29912950
Retinal detachment	16.64	16.35	21	25383	5039	29922035
Atrophy of globe	16.53	16.35	4	25400	24	29927050
Leukaemia	16.48	16.35	17	25387	3280	29923794
Enteritis	16.42	16.35	24	25380	6621	29920453
Dysarthria	16.41	16.35	3	25401	30487	29896587
Electrocardiogram QT prolonged	16.38	16.35	5	25399	35830	29891244

Pharmacologic Action:

Source	Code	Description
ATC	L01AA03	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS ALKYLATING AGENTS Nitrogen mustard analogues
FDA MoA	N0000000236	Alkylating Activity
FDA EPC	N0000175558	Alkylating Drug
MeSH PA	D000477	Alkylating Agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D018906	Antineoplastic Agents, Alkylating
MeSH PA	D007155	Immunologic Factors
MeSH PA	D007166	Immunosuppressive Agents
MeSH PA	D019653	Myeloablative Agonists
MeSH PA	D009676	Noxae
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:35705	immunosuppressant
CHEBI has role	CHEBI:50903	cancerogene
CHEBI has role	CHEBI:88188	allergenic drug

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Multiple myeloma	indication	109989006	DOID:9538
Malignant tumor of ovary	indication	363443007	DOID:2394
Allogeneic bone marrow transplantation	off-label use	58390007
Diffuse non-Hodgkin's lymphoma, large cell	off-label use	109969005
Acute hemorrhage	contraindication	8573003
Vasculitis	contraindication	31996006	DOID:865
Fibrosis of lung	contraindication	51615001	DOID:3770
Portal vein obstruction	contraindication	57348003
Hemolytic anemia	contraindication	61261009	DOID:583
Acute infectious disease	contraindication	63171007
Interstitial pneumonia	contraindication	64667001
Leukopenia	contraindication	84828003	DOID:615
Kidney disease	contraindication	90708001	DOID:557
Radiation oncology AND/OR radiotherapy	contraindication	108290001
Liver function tests abnormal	contraindication	166603001
Drug-induced hepatitis	contraindication	235876009
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Bone marrow depression	contraindication	307762000
Breastfeeding (mother)	contraindication	413712001
Granulocytopenic disorder	contraindication	417672002

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	2.27	acidic
pKa2	9.25	Basic
pKa3	4.94	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 50MG BASE/VIAL	EVOMELA	ACROTECH	N207155	March 10, 2016	RX	POWDER	INTRAVENOUS	March 10, 2023	FOR HIGH-DOSE CONDITIONING TREATMENT PRIOR TO HEMATOPOIETIC PROGENITOR (STEM) CELL TRANSPLANTATION IN PATIENTS WITH MULTIPLE MYELOMA

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
DNA	DNA			CROSS-LINKING AGENT				DRUG LABEL	DRUG LABEL
L-type amino acid transporter 1	Unclassified		LAT1_RAT		Ki	4.26		CHEMBL

External reference:

ID	Source
4020558	VUID
N0000022818	NUI
D00369	KEGG_DRUG
3223-07-2	SECONDARY_CAS_RN
4018763	VANDF
4020558	VANDF
C0025241	UMLSCUI
CHEBI:28876	CHEBI
CHEMBL852	ChEMBL_ID
CHEMBL1200863	ChEMBL_ID
CHEMBL250892	ChEMBL_ID
D008558	MESH_DESCRIPTOR_UI
460612	PUBCHEM_CID
DB01042	DRUGBANK_ID
7620	IUPHAR_LIGAND_ID
745	INN_ID
Q41OR9510P	UNII
151325	RXNORM
167596	MMSL
1789	MMSL
31570	MMSL
5038	MMSL
d00287	MMSL
002633	NDDF
004144	NDDF
387297002	SNOMEDCT_US
426388000	SNOMEDCT_US
544002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Melphalan	HUMAN PRESCRIPTION DRUG LABEL	1	47781-200	TABLET	2 mg	ORAL	ANDA	21 sections
ALKERAN	HUMAN PRESCRIPTION DRUG LABEL	1	52609-0001	TABLET, FILM COATED	2 mg	ORAL	NDA	24 sections
EVOMELA	HUMAN PRESCRIPTION DRUG LABEL	1	68152-109	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	NDA	26 sections
EVOMELA	Human Prescription Drug Label	1	72893-001	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	50 mg	INTRAVENOUS	NDA	26 sections