TAFENOQUINE SUCCINATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C24H28F3N3O3.C4H6O4
Molecular Weight	581.5807
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CCC(O)=O.COC1=NC2=C(C(C)=C1)C(OC3=CC=CC(=C3)C(F)(F)F)=C(OC)C=C2NC(C)CCCN

InChI

InChIKey=CQBKFGJRAOXYIP-UHFFFAOYSA-N

InChI=1S/C24H28F3N3O3.C4H6O4/c1-14-11-20(32-4)30-22-18(29-15(2)7-6-10-28)13-19(31-3)23(21(14)22)33-17-9-5-8-16(12-17)24(25,26)27;5-3(6)1-2-4(7)8/h5,8-9,11-13,15,29H,6-7,10,28H2,1-4H3;1-2H2,(H,5,6)(H,7,8)

HIDE SMILES / InChI

Molecular Formula	C4H6O4
Molecular Weight	118.088
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C24H28F3N3O3
Molecular Weight	463.4926
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26610844 | https://www.ncbi.nlm.nih.gov/pubmed/20837758 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210795s000lbl.pdf

Tafenoquine is anti-malaria drug originated in Walter reed army institute of research and developed by GSK and 60 Degrees Pharmaceuticals. In 2018 United States Food and Drug Administration (FDA) approved single dose tafenoquine for the radical cure (prevention of relapse) of Plasmodium vivax malaria. Tafenoquine, an 8-aminoquinoline antimalarial, is active against all the stages of Plasmodium species that include the hypnozoite (dormant stage) in the liver. Studies in vitro with the erythrocytic forms of Plasmodium falciparum suggest that tafenoquine may exert its effect by inhibiting hematin polymerization and inducing apoptotic like death of the parasite. In addition to its effect on the parasite, tafenoquine causes red blood cell shrinkage in vitro. Tafenoquine is active against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of Plasmodium species that include P. falciparum and P. vivax. The activity of tafenoquine against the pre-erythrocytic liver stages of the parasite, prevents the development of the erythrocytic forms of the parasite.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Oxidative phosphorylation 15 Target ID: map00190 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20837758	Inhibitor 8297
Plasmodium berghei 9 Target ID: CHEMBL612653 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21141892	Inhibitor 8297
Plasmodium falciparum 74 Target ID: CHEMBL364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25650255	Inhibitor 8297	217.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria 95 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	Curative		Approved 8429	ARAKODA Approved Use ARAKODA is an antimalarial indicated for the prophylaxis of malaria in patients aged 18 years and older Launch Date 2018

C_max

Value	Dose	Co-administered	Analyte	Population
147 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		TAFENOQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

AUC

Value	Dose	Co-administered	Analyte	Population
70 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		TAFENOQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

T_1/2

Value	Dose	Co-administered	Analyte	Population
16.5 day DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		TAFENOQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		TAFENOQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT

Doses

Dose	Population	Adverse events
200 mg 1 times / day multiple, oral (starting) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	healthy, 29 years (range: 17-69 years) n = 492 Health Status: healthy Age Group: 29 years (range: 17-69 years) Sex: M+F Population Size: 492 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	Other AEs: Headache, Sinus headache... Other AEs: Headache (15%) Sinus headache (15%) Migraine (15%) Tension headache (15%) Dizziness (1%) Dizziness postural (1%) Nervous system disorders (22%) Musculoskeletal and connective tissue disorders (29%) Back pain (14%) Gastrointestinal disorders (36%) Diarrhea (18%) Nausea (7%) Vomiting (5%) Psychiatric disorders (5%) Abnormal dreams (2%) Insomnia (2%) Nightmares (2%) Sleep disorder (2%) Somnambulism (2%) Anxiety disorder (1%) Panic attack (1%) Ear and labyrinth disorders (7%) Motion sickness (5%) Vertigo (5%) Vertigo positional (5%) Stress (1%) Headache (15%) Sinus headache (15%) Migraine (15%) Tension headache (15%) Dizziness (1%) Dizziness postural (1%) Nervous system disorders (22%) Musculoskeletal and connective tissue disorders (29%) Back pain (14%) Gastrointestinal disorders (36%) Diarrhea (18%) Nausea (7%) Vomiting (5%) Psychiatric disorders (5%) Abnormal dreams (2%) Insomnia (2%) Nightmares (2%) Sleep disorder (2%) Somnambulism (2%) Anxiety disorder (1%) Panic attack (1%) Ear and labyrinth disorders (7%) Motion sickness (5%) Vertigo (5%) Vertigo positional (5%) Stress (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf
200 mg 1 times / day multiple, oral (starting) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	unhealthy, 29 years (range: 17-69 years) n = 333 Health Status: unhealthy Condition: malaria Age Group: 29 years (range: 17-69 years) Sex: M+F Population Size: 333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf	Other AEs: Headache, Sinus headache... Other AEs: Headache (32%) Sinus headache (32%) Migraine (32%) Tension headache (32%) Dizziness (5%) Dizziness postural (5%) Nervous system disorders (35%) Musculoskeletal and connective tissue disorders (27%) Back pain (14%) Gastrointestinal disorders (31%) Diarrhea (5%) Nausea (5%) Vomiting (2%) ALT increased (4%) Psychiatric disorders (2%) Abnormal dreams (1%) Insomnia (1%) Nightmares (1%) Sleep disorder (1%) Somnambulism (1%) Depression (1%) Depressed mood (1%) Hemolytic anemia (<1%) Anemia (<1%) Thrombocytopenia (<1%) Hyperacusis (<1%) Meniere's disease (<1%) Hyperbilirubinemia (<1%) Jaundice cholestatic (<1%) Blood bilirubin increased (<1%) Blood creatinine increased (<1%) Glomerular filtration rate decreased (<1%) Amnesia (<1%) Coordination abnormal (<1%) Hyperesthesia (<1%) Hypoesthesia (<1%) Somnolence (<1%) Visual field defect (<1%) Urticaria (<1%) Headache (32%) Sinus headache (32%) Migraine (32%) Tension headache (32%) Dizziness (5%) Dizziness postural (5%) Nervous system disorders (35%) Musculoskeletal and connective tissue disorders (27%) Back pain (14%) Gastrointestinal disorders (31%) Diarrhea (5%) Nausea (5%) Vomiting (2%) ALT increased (4%) Psychiatric disorders (2%) Abnormal dreams (1%) Insomnia (1%) Nightmares (1%) Sleep disorder (1%) Somnambulism (1%) Depression (1%) Depressed mood (1%) Hemolytic anemia (<1%) Anemia (<1%) Thrombocytopenia (<1%) Hyperacusis (<1%) Meniere's disease (<1%) Hyperbilirubinemia (<1%) Jaundice cholestatic (<1%) Blood bilirubin increased (<1%) Blood creatinine increased (<1%) Glomerular filtration rate decreased (<1%) Amnesia (<1%) Coordination abnormal (<1%) Hyperesthesia (<1%) Hypoesthesia (<1%) Somnolence (<1%) Visual field defect (<1%) Urticaria (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210607lbl.pdf
400 mg 1 times / day multiple, oral (starting) Studied dose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	unhealthy, 34 years (range: 18-50 years) n = 62 Health Status: unhealthy Condition: malaria Age Group: 34 years (range: 18-50 years) Sex: M+F Population Size: 62 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf
200 mg 1 times / day multiple, oral (starting) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	unhealthy, adolescents; adults n = 825 Health Status: unhealthy Condition: malaria Age Group: adolescents; adults Sex: M+F Population Size: 825 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	Disc. AE: ALT increased, Hemoglobin decreased... Other AEs: ALT increased, Hemoglobin decreased... AEs leading to discontinuation/dose reduction: ALT increased (0.7%) Hemoglobin decreased (0.4%) GFR decreased (0.2%) Malaria (0.5%) Pneumonia (0.1%) Viral infection (0.1%) Fall (0.1%) Joint injury (0.1%) Meniscus lesion (0.1%) Thermal burn (0.1%) Soft tissue injury (0.1%) Upper limb fracture (0.1%) Upper abdominal pain (0.1%) Irritable bowel syndrome (0.1%) Musculoskeletal pain (0.1%) Depression (0.1%) Metamorphopsia (0.1%) Night blindness (0.1%) Rash (0.1%) Lactose intolerance (0.1%) Hyperbilirubinemia (0.1%) Other AEs: ALT increased (0.7%) Hemoglobin decreased (0.4%) GFR decreased (0.2%) Malaria (0.5%) Pneumonia (0.1%) Viral infection (0.1%) Fall (0.1%) Joint injury (0.1%) Meniscus lesion (0.1%) Thermal burn (0.1%) Soft tissue injury (0.1%) Upper limb fracture (0.1%) Upper abdominal pain (0.1%) Irritable bowel syndrome (0.1%) Musculoskeletal pain (0.1%) Depression (0.1%) Metamorphopsia (0.1%) Night blindness (0.1%) Rash (0.1%) Lactose intolerance (0.1%) Hyperbilirubinemia (0.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf
600 mg 1 times / day multiple, oral Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	healthy n = 36 Health Status: healthy Sex: M+F Population Size: 36 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf
600 mg 1 times / week multiple, oral Highest studied dose Dose: 600 mg, 1 times / week Route: oral Route: multiple Dose: 600 mg, 1 times / week Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	healthy n = 36 Health Status: healthy Sex: M+F Population Size: 36 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf
600 mg single, oral Highest studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	healthy n = 75 Health Status: healthy Sex: M Population Size: 75 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf
400 mg 1 times / day multiple, oral Studied dose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	healthy n = 52 Health Status: healthy Sex: unknown Population Size: 52 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (1 patient) Vomiting (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf
600 mg single, oral Studied dose Dose: 600 mg Route: oral Route: single Dose: 600 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	healthy n = 52 Health Status: healthy Sex: unknown Population Size: 52 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf	Other AEs: CPK increased, Hemoglobin increased... Other AEs: CPK increased (4%) Hemoglobin increased (2%) Hypersensitivity (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8 911 OCT2 647 MATE1 306 MATE2 263 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706 BCRP 699 P-gp 1461 CYP2A6 707 CYP2C19 1478 CYP2E1 882 CYP4A9/11 37	OATP1B1 406 OATP1B3 350 P-gp 1537 BCRP 561

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP4A9/11 37	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=250 Page: 250.0	no [IC50 18 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=250 Page: 250.0	no [IC50 54 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=250 Page: 250.0	no [IC50 7.1 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=250 Page: 250.0	no [IC50 81 uM]
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	no [IC50 >25 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	no [IC50 >25 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	no [IC50 >25 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	no [IC50 >25 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes [IC50 0.282 uM]
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes [IC50 0.632 uM]
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes [IC50 1.99 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes [IC50 15 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes [IC50 5.61 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes [Ki 15 uM]	no (co-administration study) Comment: Subsequent clinical DDI studies demonstrated no clinically significant effects of TQ on the PK of desipramine (CYP2D6 substrate) (Study SB252263/015), caffeine (CYP1A2 substrate), midazolam (CYP3A4 substrate), and flurbiprofen (CYP2C9 substrate) (Study SB252263/040). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes [Ki 5.2 uM]	no (co-administration study) Comment: Subsequent clinical DDI studies demonstrated no clinically significant effects of TQ on the PK of desipramine (CYP2D6 substrate) (Study SB252263/015), caffeine (CYP1A2 substrate), midazolam (CYP3A4 substrate), and flurbiprofen (CYP2C9 substrate) (Study SB252263/040). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes	no (co-administration study) Comment: Subsequent clinical DDI studies demonstrated no clinically significant effects of TQ on the PK of desipramine (CYP2D6 substrate) (Study SB252263/015), caffeine (CYP1A2 substrate), midazolam (CYP3A4 substrate), and flurbiprofen (CYP2C9 substrate) (Study SB252263/040). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes	no (co-administration study) Comment: Subsequent clinical DDI studies demonstrated no clinically significant effects of TQ on the PK of desipramine (CYP2D6 substrate) (Study SB252263/015), caffeine (CYP1A2 substrate), midazolam (CYP3A4 substrate), and flurbiprofen (CYP2C9 substrate) (Study SB252263/040). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=73 Page: 73.0	yes
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=73 Page: 73.0	yes
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=73 Page: 73.0	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=73 Page: 73.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210607Orig1s000MultidisciplineR.pdf#page=39 Page: 39.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA008UWB	https://www.aablocks.com/goods/Goods/detail?id=AA008UWB
Ambeed	A299706	https://www.ambeed.com/products/106635-80-7.html
BLD Pharm	BD763954	http://www.bldpharm.com/products/106635-80-7.html
CSNpharm	CSN20176	https://www.csnpharm.com/products/tafenoquine.html
Chem Scene	CS-0042381	http://www.chemscene.com/106635-80-7.html
Chemspace	CSSB00020675268	https://chem-space.com/CSSB00020675268
DC Chemicals	DC21609	http://www.dcchemicals.com/product_show-DC21609.html
Excenen	EX-A3146	https://www.excenen.com/searchresultlist.php?id=106635-80-7
Finetech	FT-0775258	https://www.finetechnology-ind.com/prod/detail/pub/106635-80-7.html
MedChem Express	HY-111529	https://www.medchemexpress.com/Tafenoquine.html
MolPort	MolPort-046-683-250	https://www.molport.com/shop/molecule-link/MolPort-046-683-250
Smolecule	S544419	http://www.smolecule.com/products/s544419
Smolecule	S750577	https://www.smolecule.com/products/s750577
Synblock Inc	SB16555	http://www.synblock.com/product/106635-80-7.html
THE BioTek	bt-283108	https://www.thebiotek.com/product/inhibitors/bt-283108
THE BioTek	bt-312092	https://www.thebiotek.com/product/others/bt-312092
eNovation Chemicals	D674102	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674102

PubMed

Title	Date	PubMed
Isolation and characterization of rat lung Pneumocystis carinii gp120.	1991 Nov-Dec	1818123
8-aminoquinolines effective against Pneumocystis carinii in vitro and in vivo.	1993 Oct	8257140
8-Aminoquinolines active against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization.	1999 Mar	10049273
Experiences with malaria chemoprophylaxis in Dutch troops.	2001	11584661
Malaria chemoprophylaxis in the age of drug resistance. II. Drugs that may be available in the future.	2001 Aug 1	11438908
Malaria chemoprophylaxis in the age of drug resistance. I. Currently recommended drug regimens.	2001 Jul 15	11418883
In vitro activity of tafenoquine alone and in combination with artemisinin against Plasmodium falciparum.	2002 Jul	12363062
Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?	2002 Mar 25	11914150
In-vitro interaction of tafenoquine and chloroquine in Plasmodium falciparum from northwestern Thailand.	2003	15508777
Blood schizontocidal activity of WR 238605 (Tafenoquine) against Plasmodium cynomolgi and Plasmodium fragile infections in rhesus monkeys.	2003 Apr	12711101
Military aviators, special operations forces, and causal malaria prophylaxis.	2003 Dec	14719625
Plasma concentrations of tafenoquine, a new long-acting antimalarial agent, in thai soldiers receiving monthly prophylaxis.	2003 Dec 15	14689348
Efficacy of a 14-day primaquine regimen in preventing relapses in patients with Plasmodium vivax malaria in Mumbai, India.	2003 Jul-Aug	15259476
Transmission-blocking activity of tafenoquine (WR-238605) and artelinic acid against naturally circulating strains of Plasmodium vivax in Thailand.	2003 Nov	14695093
New antimalarial drugs.	2003 Nov 10	14613157
Malaria chemoprophylaxis: when should we use it and what are the options?	2004 Feb	15482177
Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse.	2004 Oct 15	15486831
Modern malaria chemoprophylaxis.	2005	16225366
[Malaria chemoprophylaxis in traveling children].	2005 Jan	15653056
Drug development papers in PLoS Medicine: how we try to spot a winner.	2006 Dec	17526082
A plant-derived morphinan as a novel lead compound active against malaria liver stages.	2006 Dec	17194195
8-Aminoquinolines: future role as antiprotozoal drugs.	2006 Dec	17075340
Antimalarial efficacy and drug interactions of the novel semi-synthetic endoperoxide artemisone in vitro and in vivo.	2007 Apr	17337512
Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed?	2007 Feb 16	17306014
Tafenoquine for the treatment of recurrent Plasmodium vivax malaria.	2007 Mar	17360873
Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis.	2007 Mar	16814823
Tafenoquine: a promising new antimalarial agent.	2007 May	17461742
Selective plasma protein binding of antimalarial drugs to alpha1-acid glycoprotein.	2008 Apr 1	18289858
Prevalence of contraindications to mefloquine use among USA military personnel deployed to Central Asia.	2008 Feb 11	18267019
How antimalarial drug resistance affects post-treatment prophylaxis.	2008 Jan 11	18186948
The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific.	2008 Nov	18541280
A randomized, double-blind, safety and tolerability study to assess the ophthalmic and renal effects of tafenoquine 200 mg weekly versus placebo for 6 months in healthy volunteers.	2009 Aug	19635898
Plasmodium berghei ANKA: selection of resistance to piperaquine and lumefantrine in a mouse model.	2009 Jul	19318094
Primaquine revisited six decades after its discovery.	2009 Mar	18930565
Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.	2009 Nov 18	19924309
Structural modifications of quinoline-based antimalarial agents: Recent developments.	2010 Apr	21814435
Antileishmanial and antitrypanosomal activities of the 8-aminoquinoline tafenoquine.	2010 Dec	20837750
Establishment of an in vitro assay for assessing the effects of drugs on the liver stages of Plasmodium vivax malaria.	2010 Dec 9	21151554
In vitro selection of Plasmodium falciparum drug-resistant parasite lines.	2010 Mar	20022938
Operational strategies to achieve and maintain malaria elimination.	2010 Nov 6	21035841

Patents

Sample Use Guides

In Vivo Use Guide

Loading regimen: 200 mg (2 of the 100 mg tablets) once daily for 3 days Maintenance regimen: 200 mg (2 of the 100 mg tablets) once weekly – start 7 days after the last loading regimen dose Terminal prophylaxis regimen: 200 mg (2 of the 100 mg tablets) one-time 7 days after the last maintenance dose

Route of Administration: Oral

In Vitro Use Guide

After 72 h of tafenoquine exposure, proliferation of L. donovani and Leishmania major promastigotes was inhibited at the micromolar range in a dose-dependent manner, with 50% effective concentrations (EC50s) of 5.6 ± 1.0 uM and 5.3 ± 2.1 uM for L. donovani.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:21:26 GMT 2023` Edited by `admin` on `Sat Dec 16 05:21:26 GMT 2023`
Record UNII	DL5J0B8VSS
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TAFENOQUINE SUCCINATE

Official Name

English

BUTANEDIOIC ACID, COMPD. WITH N4-(2,6-DIMETHOXY-4-METHYL-5-(3-(TRIFLUOROMETHYL)PHENOXY)-8-QUINOLINYL)-1,4-PENTANEDIAMINE (1:1)

Common Name

English

WR-238605

Code

English

(4RS)-N4-{2,6-Dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl}pentane-1,4-diamine butanedioate

Systematic Name

English

KRINTAFEL

Brand Name

English

TAFENOQUINE SUCCINATE [USAN]

Common Name

English

TAFENOQUINE SUCCINATE [MI]

Common Name

English

Tafenoquine succinate [WHO-DD]

Common Name

English

ARAKODA

Brand Name

English

SB-252263-AX

Code

English

TAFENOQUINE SUCCINATE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C271