Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H26ClN3.2C5H4N2O4 |
Molecular Weight | 632.065 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)C1=CC(=O)NC(=O)N1.OC(=O)C2=CC(=O)NC(=O)N2.CCN(CC)CCCC(C)NC3=CC=NC4=CC(Cl)=CC=C34
InChI
InChIKey=IUEFAROUKVNKKL-UHFFFAOYSA-N
InChI=1S/C18H26ClN3.2C5H4N2O4/c1-4-22(5-2)12-6-7-14(3)21-17-10-11-20-18-13-15(19)8-9-16(17)18;2*8-3-1-2(4(9)10)6-5(11)7-3/h8-11,13-14H,4-7,12H2,1-3H3,(H,20,21);2*1H,(H,9,10)(H2,6,7,8,11)
Molecular Formula | C5H4N2O4 |
Molecular Weight | 156.0963 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C18H26ClN3 |
Molecular Weight | 319.872 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
Chloroquine (brand name Aralen) is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. In addition, chloroquine is in clinical trials as an investigational antiretroviral in humans with HIV-1/AIDS and as a potential antiviral agent against chikungunya fever. The mechanism of plasmodicidal action of chloroquine is not completely certain. However, is existed theory, that like other quinoline derivatives, it is thought to inhibit heme polymerase activity. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a non-toxic molecule. Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form what is known as the FP-Chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6129306
Curator's Comment: Known to be CNS penetrant in rat. Human data not available.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22411634
Curator's Comment: # Hans Andersag and coworkers at the Bayer laboratories
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL613897 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14967191 |
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Target ID: P13774 Gene ID: NA Gene Symbol: NA Target Organism: Plasmodium falciparum Sources: https://www.ncbi.nlm.nih.gov/pubmed/10187806 |
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Target ID: CHEMBL364 |
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Target ID: CHEMBL613897 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14967191 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | ARALEN Approved UseARALEN is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. ARALEN does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum. Launch Date1949 |
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Curative | ARALEN Approved UseARALEN is indicated for the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis. ARALEN does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum. Launch Date1949 |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
700 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18594802/ |
5 mg/kg 1 times / day multiple, oral dose: 5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
CHLOROQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
134087 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18594802/ |
5 mg/kg 1 times / day multiple, oral dose: 5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
CHLOROQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
209 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18594802/ |
5 mg/kg 1 times / day multiple, oral dose: 5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
CHLOROQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
45% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18594802/ |
5 mg/kg 1 times / day multiple, oral dose: 5 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered: |
CHLOROQUINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
3 g single, oral Overdose |
unknown, 14 years n = 1 Health Status: unknown Age Group: 14 years Sex: F Population Size: 1 Sources: |
Other AEs: Cardiac arrest... |
600 mg 2 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
pregnant, 20.7 years n = 300 Health Status: pregnant Condition: malaria Age Group: 20.7 years Sex: F Population Size: 300 Sources: |
Other AEs: Dizziness, Vomiting... Other AEs: Dizziness (19%) Sources: Vomiting (17%) Palpitations (5%) Headache (6%) Nausea (5%) Abdominal pain (2%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Cardiac arrest | 3 g single, oral Overdose |
unknown, 14 years n = 1 Health Status: unknown Age Group: 14 years Sex: F Population Size: 1 Sources: |
|
Vomiting | 17% | 600 mg 2 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
pregnant, 20.7 years n = 300 Health Status: pregnant Condition: malaria Age Group: 20.7 years Sex: F Population Size: 300 Sources: |
Dizziness | 19% | 600 mg 2 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
pregnant, 20.7 years n = 300 Health Status: pregnant Condition: malaria Age Group: 20.7 years Sex: F Population Size: 300 Sources: |
Abdominal pain | 2% | 600 mg 2 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
pregnant, 20.7 years n = 300 Health Status: pregnant Condition: malaria Age Group: 20.7 years Sex: F Population Size: 300 Sources: |
Nausea | 5% | 600 mg 2 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
pregnant, 20.7 years n = 300 Health Status: pregnant Condition: malaria Age Group: 20.7 years Sex: F Population Size: 300 Sources: |
Palpitations | 5% | 600 mg 2 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
pregnant, 20.7 years n = 300 Health Status: pregnant Condition: malaria Age Group: 20.7 years Sex: F Population Size: 300 Sources: |
Headache | 6% | 600 mg 2 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
pregnant, 20.7 years n = 300 Health Status: pregnant Condition: malaria Age Group: 20.7 years Sex: F Population Size: 300 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | no (co-administration study) Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4 |
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no | no (co-administration study) Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4 |
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no | no (co-administration study) Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4 |
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no | no (co-administration study) Comment: chloroquine did not affect the activities of CYP1A2, CYP2C19, CYP2E1, CYP3A4 |
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yes [IC50 1096 uM] | ||||
yes [IC50 2.5 uM] | ||||
yes [Ki 12 uM] | weak (co-administration study) Comment: selective inhibiton; Chloroquine produced a reduction in the metabolism of debrisoquine as evaluated by the debrisoquine recovery ratio, a measure of CYP2D6 activity. This reduction was progressive from the first to the seventh dose. This decrease in metabolism was modest (about 7% after the first dose and about 18% after seven doses) but statistically significant |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes | yes (co-administration study) Comment: Concomitant administration of a single dose of chloroquine and cimetidine daily starting 4 days prior to chloroquine, resulted in a 50% increase in chloroquine half-life, associated with a 50% decrease in its clearance.Since the AUC of desethylchloroquine decreased by 47%, cimetidine probably decreased chloroquine clearance by inhibiting its hepatic desethylation. |
|||
yes | yes (co-administration study) Comment: Concomitant administration of a single dose of chloroquine and cimetidine daily starting 4 days prior to chloroquine, resulted in a 50% increase in chloroquine half-life, associated with a 50% decrease in its clearance.Since the AUC of desethylchloroquine decreased by 47%, cimetidine probably decreased chloroquine clearance by inhibiting its hepatic desethylation. |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/14729380/ Page: 44.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Tissue and blood concentrations of chloroquine following chronic administration in the rat. | 1982 Nov |
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Kinetics of the uptake and elimination of chloroquine in children with malaria. | 1982 Oct |
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Drug-induced haemolysis and renal failure in children with glucose-6-phosphate dehydrogenase deficiency in Central Asia. | 1990 |
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Inhibition of human immunodeficiency virus infectivity by chloroquine. | 1990 Apr |
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Amrinone for refractory cardiogenic shock following chloroquine poisoning. | 1991 |
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Persisting chloroquine-induced myasthenia? | 1991 |
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Occurrence of chloroquine-induced psychotic manifestations in children with malaria. | 1992 |
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Seizures associated with chloroquine therapy. | 1992 Aug |
|
Chloroquine related complete heart block with blindness: case report. | 1992 Jan |
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The effect of EGb 761 on the doxorubicin cardiomyopathy. | 1999 |
|
Calcitriol-mediated hypercalcaemia and increased interleukins in a patient with sarcoid myopathy. | 1999 |
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Potential inhibitors of HIV integrase. | 1999 Apr-May |
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[Neuromuscular complications of long-term treatment of inflammatory diseases. 3 cases]. | 1999 Dec |
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Cadmium-mediated oxidative stress in kidney proximal tubule cells induces degradation of Na+/K(+)-ATPase through proteasomal and endo-/lysosomal proteolytic pathways. | 1999 Oct |
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Multifocal ERG in chloroquine retinopathy: regional variance of retinal dysfunction. | 2000 Jan |
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In vivo antimalarial activity of the beta-carboline alkaloid manzamine A. | 2000 Jun |
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Coma in a patient with Alzheimer's disease taking low dose trazodone and gingko biloba. | 2000 May |
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Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide. | 2001 Jul 31 |
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Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-alpha. | 2001 Oct 1 |
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Syncope following oral chloroquine administration in a hypertensive patient controlled on amlodipine. | 2002 Apr |
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Cardiac damage from chronic use of chloroquine: a case report and review of the literature. | 2002 Jul |
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[Many travellers suffer of side-effects of malaria prophylaxis]. | 2002 Jun 27 |
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The first molecular evidence that autophagy relates rimmed vacuole formation in chloroquine myopathy. | 2002 May |
|
Side effects of and compliance with malaria prophylaxis in children. | 2002 Nov-Dec |
|
EGb 761 is a neuroprotective agent against beta-amyloid toxicity. | 2002 Sep |
|
Control of mammary tumor cell growth in vitro by novel cell differentiation and apoptosis agents. | 2002 Sep |
|
Chloroquine cardiotoxicity: clinicopathologic features in three patients and comparison with three patients with Fabry disease. | 2002 Sep-Oct |
|
Chloroquine-induced phospholipidosis of the kidney mimicking Fabry's disease: case report and review of the literature. | 2003 Mar |
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Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus. | 2003 Nov |
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Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. | 2003 Sep |
|
Heart transplantation in a patient with chloroquine-induced cardiomyopathy. | 2004 Feb |
|
Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells. | 2004 Jul |
|
Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. | 2004 Jun 11 |
|
Seizure associated with chloroquine therapy in a patient with systemic lupus erythematosus. | 2004 Sep |
|
Ginkgo biloba leaf extract (EGb 761) enhances catalepsy induced by haloperidol and L-nitroarginine in mice. | 2005 Nov |
|
Images in cardiovascular medicine. Contrast-enhanced magnetic resonance imaging of a patient with chloroquine-induced cardiomyopathy confirmed by endomyocardial biopsy. | 2006 Aug 22 |
|
CpG-B oligodeoxynucleotide promotes cell survival via up-regulation of Hsp70 to increase Bcl-xL and to decrease apoptosis-inducing factor translocation. | 2006 Dec 15 |
|
[Cytochrome P-450 and the response to antimalarial drugs]. | 2006 Jan |
|
Mefloquine toxicity presenting with polyneuropathy - a report of two cases in India. | 2006 Jun |
|
Tetrahydrocurcumin: effect on chloroquine-mediated oxidative damage in rat kidney. | 2006 Nov |
|
Cardiomyopathy related to antimalarial therapy with illustrative case report. | 2007 |
|
Chloroquine-induced recurrent psychosis. | 2007 Jul-Aug |
|
Effects of CpG-B ODN on the protein expression profile of swine PBMC. | 2007 Nov-Dec |
|
A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru. | 2007 Oct 31 |
|
Autophagy inhibitors chloroquine and LY294002 enhance temozolomide cytotoxicity on cutaneous melanoma cell lines in vitro. | 2017 Mar |
Sample Use Guides
The dosage of chloroquine phosphate is often expressed in terms of equivalent
chloroquine base. Each 500 mg tablet of ARALEN (chloroquine phosphate) contains the equivalent of 300 mg chloroquine base. In infants and children the dosage is preferably calculated by body weight.
Malaria: Suppression—Adult Dose: 500 mg (= 300 mg base) on exactly the same day of each week. Pediatric Dose: The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight. If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this in adults, an initial double (loading) dose of 1 g (= 600 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.
For Treatment of Acute Attack. Adults: An initial dose of 1 g (=600 mg base) followed by an additional 500 mg (= 300 mg base) after six to eight hours and a single dose of 500 mg (= 300 mg base) on each of two consecutive days. This represents a total dose of 2.5 g chloroquine phosphate or 1.5 g base in three days. The dosage for adults of low body weight and for infants and children should be determined as follows: First dose: 10 mg base per kg (but not exceeding a single dose of 600 mg base) Second dose: (6 hours after first dose) 5 mg base per kg (but not exceeding a single dose of 300 mg base) Third dose: (24 hours after first dose) 5mg base per kg Fourth dose: (36 hours after first dose) 5 mg base per kg For radical cure of vivax and malariae malaria concomitant therapy with an 8-aminoquinoline compound is necessary. Extraintestinal Amebiasis: Adults, 1 g (600 mg base) daily for two days, followed by 500 mg (300 mg base) daily for at least two to three weeks. Treatment is usually combined with an effective intestinal amebicide.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19194831
Chloroquine inhibited mouse colon cancer cell line CT26 cells proliferation by concentration- and time-dependent manner. This effect was associated with apoptosis induction and decreased level of phosphorylated p42/44 mitogen-activated protein kinase and phosphorylated Akt. The cytotoxicity of chloroquine on CT26 cells was determined by the MTT assay. Cells were seeded in 96-well plates at the density of 2000/well and cultured for 24 hr, followed by chloroquine treatment (100, 50, 25, 12.5, 6.25, and 3.125 μ mol/L) for 24, 48, and 72 hr, respectively.
Substance Class |
Chemical
Created
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admin
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Edited
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by
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on
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Record UNII |
1RO28BA0DO
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Record Status |
Validated (UNII)
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Record Version |
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DTXSID00936779
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83835
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C000660
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16301-30-7
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SUB01236MIG
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1RO28BA0DO
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100000084716
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240-389-6
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Related Record | Type | Details | ||
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ENANTIOMER -> RACEMATE | |||
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |