Natural Product (NP) Details

General Information of the NP (ID: NP6495)
Name
Fluoroorotic acid
Synonyms
5-Fluoroorotic acid; 703-95-7; 5-fluoro-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid; 5-Fluoroorotate; Fluoroorotic acid; Orotic acid, 5-fluoro-; 5-Fluorouracil-4-carboxylic acid; 5-FOA; ENT-26398; NSC 31712; Ro 2-9945; UNII-7IA9OUC93E; WR 152520; MLS000737636; 5-fluoro-2,4-dioxo-1H-pyrimidine-6-carboxylic acid; 4-Pyrimidinecarboxylic acid, 5-fluoro-1,2,3,6-tetrahydro-2,6-dioxo-; 7IA9OUC93E; Fluoroorotic Acid, Ultra Pure; FOA; 5-Fluorouracil-6-carboxylic Acid; 1,2,3,6-Tetrahydro-2,6-dioxo-5-fluoro-4-pyrimidinecarboxylic acid; MFCD00042526; SMR000393806; 4-Pyrimidinecarboxylic acid, 1,2,3,6-tetrahydro-2,6-dioxo-5-fluoro-; 5-Fluoro orotic acid; 5-Fluoroorotic acid (VAN); EINECS 211-876-0; 5-fluoro-2,6-dioxo-1,3-dihydropyrimidine-4-carboxylic acid; AI3-26398; 5-Fluoroortic acid; FOT; 174.09 (anhydrous); C5H3FN2O4.xH2O; 5-Fluoroorotic acid;5-FOA; SCHEMBL44527; WLN: T6VMVMJ EVQ FF; cid_69711; CHEMBL1232805; BDBM47470; 5-Fluoroorotic acid, 98.0%+; DTXSID90220573; 5-fluorouracil-4-carboxylic acid;; HMS2759G19; ACT03077; EBD39533; NSC31712; ZINC1663959; 5-Fluoro-1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid; ANW-46244; NSC-31712; SBB066881; AKOS005207200; CS-W017535; 4-Pyrimidinecarboxylic acid, 5-fluoro-1,2,3,6-tetrahydro-2,6-dioxo-, monohydrate; 5-Fluorouracil-4-carboxylic acid hydrate; NCGC00246927-01; Orotic acid, 5-fluoro- (VAN) (8CI); AC-10068; AS-14168; K187; SY001827; AB0014081; F0382; FT-0620427; ST50405211; F-6300; M-2738; 45988-EP2298735A1; 45988-EP2311807A1; 703F957; 2,6-Dihydroxy-5-fluoropyrimidine-4-carboxylic acid; 5-fluoro-2,4-diketo-1H-pyrimidine-6-carboxylic acid; Q18207160; 1,3,6-Tetrahydro-2,6-dioxo-5-fluoro-4-pyrimidinecarboxylic acid; 4-Pyrimidinecarboxylic acid,2,3,6-tetrahydro-2,6-dioxo-5-fluoro-; 5-fluoranyl-2,4-bis(oxidanylidene)-1H-pyrimidine-6-carboxylic acid; 5-Fluoro-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinecarboxylic acid; 5-Fluoro-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carboxylic acid; 4-Pyrimidinecarboxylic acid, 5-fluoro-1,2,3,6-tetrahydro-2,6-dioxo- (9CI)
    Click to Show/Hide
Species Origin Homo sapiens ...     Click to Show/Hide
Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Disease Aspergillosis [ICD-11: 1F20] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.644
 
MDCK Permeability
 -4.767
 
PAMPA
 +++
 
HIA
 ++
 
Distribution
VDss
 -0.538
 
PPB
 50.1%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - - -
HLM Stability
 - - -
 
Excretion
CLplasma
 2.155
 
T1/2
 2.175
Toxicity
DILI
 +++
 
Rat Oral Acute Toxicity
 +
 
FDAMDD
 - - -
 
Respiratory
 ++
 
Human Hepatotoxicity
 +++
 
Ototoxicity
 +++
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 +++
 
Hematotoxicity
 +
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
    Click to Show/Hide
    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C5H3FN2O4
PubChem CID
69711
Canonical SMILES
C1(=C(NC(=O)NC1=O)C(=O)O)F
InChI
1S/C5H3FN2O4/c6-1-2(4(10)11)7-5(12)8-3(1)9/h(H,10,11)(H2,7,8,9,12)
InChIKey
SEHFUALWMUWDKS-UHFFFAOYSA-N
CAS Number
CAS 703-95-7
TTD Drug ID
D0E2WX
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Uftoral + Oxaliplatin     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    In-vivo Model Human colorectal HT29 cell xenografts (1*106 cells) were transplanted s.c. into the hind limb of each animal (Female BALB/c nude mice (nu+/nu+) aged 6 weeks).
                    Experimental
                    Result(s)		 Combined treatment (UFT/FA+oxaliplatin) reduced tumor weight by 39% compared to oxaliplatin alone (p<0.05) or UFT/FA (p<0.05).
          Oxaliplatin + 5-fluorouracil     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 Combination chemotherapy with oxaliplatin, 5-FU, and FA is an active and well-tolerated regimen as first-line treatment in patients with metastatic or recurrent gastric cancer.
          Cisplatin + 5-fluorouracil     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 Weekly administration of 5-FU/FA/cisplatin is an active and well-tolerated regimen. Toxicity is manageable and allows chemotherapy on an outpatient basis without hydration program as required when cisplatin is used at the dose of 50 mg/m2.
          Raltitrexed + 5-fluorouracil     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model LoVo CVCL_0399 Colon adenocarcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Histone deacetylase inhibitor NVP-LAQ824 sensitizes human nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation.
          Methioninase + 5-fluorouracil     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model CCRF-CEM CVCL_0207 T acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Methioninase in combination with 5-fluorouracil and folinic acid showed cytotoxic synergism in CCRF-CEM.
Target and Pathway
Target(s) Plasmodium dihydroorotase (Malaria dho)  Molecule Info  [7]
Plasmodium dihydroorotate dehydrogenase (Malaria DHOdehase)  Molecule Info  [7]
KEGG Pathway Pyrimidine metabolism Click to Show/Hide
2 Metabolic pathways
Pathwhiz Pathway Pyrimidine Metabolism Click to Show/Hide
Reactome Pyrimidine biosynthesis Click to Show/Hide
WikiPathways Metabolism of nucleotides Click to Show/Hide
References
Reference 1 Antifungal Siderophore Conjugates for Theranostic Applications in Invasive Pulmonary Aspergillosis Using Low-Molecular TAFC Scaffolds. J Fungi (Basel). 2021 Jul 14;7(7):558.
Reference 2 Synergistic antitumoral activity of combined UFT, folinic acid and oxaliplatin against human colorectal HT29 cell xenografts in athymic nude mice. Anticancer Drugs. 2000 Aug;11(7):579-82.
Reference 3 Efficacy and safety of oxaliplatin, 5-Fluorouracil, and folinic Acid combination chemotherapy as first-line treatment in metastatic or recurrent gastric cancer. Cancer Res Treat. 2011 Sep;43(3):154-9.
Reference 4 Treatment of advanced digestive non-colon cancer with a weekly 24-h infusion of high-dose 5-fluorouracil modulated by folinic acid and cisplatin: an easy-to-use and well-tolerated combination. Anticancer Drugs. 2004 Aug;15(7):725-8.
Reference 5 Histone deacetylase inhibitor NVP-LAQ824 sensitizes human nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation. Anticancer Drugs. 2007 Aug;18(7):793-800.
Reference 6 Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid. Biochem Pharmacol. 2001 Apr 1;61(7):867-76.
Reference 7 Antimalarial activity of orotate analogs that inhibit dihydroorotase and dihydroorotate dehydrogenase. Biochem Pharmacol. 1992 Mar 17;43(6):1295-301.
 Download Picture         KEGG Link