NPASS Compound

Structure

NPC489650 OpenBabel06302215362D 39 42 0 0 0 0 0 0 0 0999 V2000 -4.5000 -1.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5000 -0.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -0.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -1.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5000 -1.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 3.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 5.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 3.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 1 0 0 0 0 2 4 1 0 0 0 0 2 5 1 0 0 0 0 5 10 2 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 7 8 1 0 0 0 0 8 9 2 0 0 0 0 8 11 1 0 0 0 0 9 10 1 0 0 0 0 11 12 2 0 0 0 0 11 13 2 0 0 0 0 11 14 1 0 0 0 0 14 15 1 0 0 0 0 15 26 2 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 16 31 1 0 0 0 0 17 18 1 0 0 0 0 17 27 1 0 0 0 0 18 19 2 0 0 0 0 19 20 1 0 0 0 0 19 26 1 0 0 0 0 20 25 2 0 0 0 0 20 21 1 0 0 0 0 21 22 2 0 0 0 0 22 23 1 0 0 0 0 23 24 2 0 0 0 0 24 25 1 0 0 0 0 27 28 1 0 0 0 0 28 29 1 0 0 0 0 29 30 1 0 0 0 0 31 32 1 0 0 0 0 32 37 2 0 0 0 0 32 33 1 0 0 0 0 33 34 2 0 0 0 0 34 35 1 0 0 0 0 35 36 2 0 0 0 0 36 37 1 0 0 0 0 37 38 1 0 0 0 0 38 39 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	551.18
Volume:	535.919
LogP:	3.266
LogD:	2.754
LogS:	-4.638
# Rotatable Bonds:	10
TPSA:	148.88
# H-Bond Aceptor:	11
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.318
Synthetic Accessibility Score:	3.184
Fsp3:	0.259
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.892
MDCK Permeability:	3.1831856176722795e-05
Pgp-inhibitor:	0.869
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.018
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012
Plasma Protein Binding (PPB):	98.54375457763672%
Volume Distribution (VD):	0.637
Pgp-substrate:	1.4562931060791016%

ADMET: Metabolism

CYP1A2-inhibitor:	0.969
CYP1A2-substrate:	0.214
CYP2C19-inhibitor:	0.869
CYP2C19-substrate:	0.151
CYP2C9-inhibitor:	0.958
CYP2C9-substrate:	0.863
CYP2D6-inhibitor:	0.937
CYP2D6-substrate:	0.075
CYP3A4-inhibitor:	0.938
CYP3A4-substrate:	0.908

ADMET: Excretion

Clearance (CL):	0.988
Half-life (T1/2):	0.337

ADMET: Toxicity

hERG Blockers:	0.046
Human Hepatotoxicity (H-HT):	0.82
Drug-inuced Liver Injury (DILI):	0.994
AMES Toxicity:	0.014
Rat Oral Acute Toxicity:	0.609
Maximum Recommended Daily Dose:	0.391
Skin Sensitization:	0.102
Carcinogencity:	0.762
Eye Corrosion:	0.003
Eye Irritation:	0.011
Respiratory Toxicity:	0.204

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC489650

Natural Product ID:	NPC489650
*Common Name:**	GJPICJJJRGTNOD-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	GJPICJJJRGTNOD-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C27H29N5O6S/c1-27(2,3)18-10-12-19(13-11-18)39(34,35)32-23-22(38-21-9-6-5-8-20(21)36-4)26(37-17-16-33)31-25(30-23)24-28-14-7-15-29-24/h5-15,33H,16-17H2,1-4H3,(H,30,31,32)
SMILES:	CC(C)(C)c1ccc(cc1)S(=O)(=O)Nc1c(c(nc(c2ncccn2)n1)OCCO)Oc1ccccc1OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	104865
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001346] Diazines [CHEMONTID:0000075] Pyrimidines and pyrimidine derivatives [CHEMONTID:0001978] Bipyrimidines and oligopyrimidines

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15921416]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	subtidal zone (0-2 m) off the southwestern shore of Jeju Island, Korea	2003-Apr	PMID[18817444]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19006667]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21377877]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28720331]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
EC50	4
IC50	35
Kd	4
Ki	6
Others	20

Activity Type	# Activity
Individual Protein	47
NON-MOLECULAR	1
Organism	8
Others	9
SINGLE PROTEIN	3
Tissue	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3951	Individual Protein	Endothelin receptor ET-A	Rattus norvegicus	Ki	=	6.5	nM	PMID[15055997]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	Ki	=	6.5	nM	PMID[9379441]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	Ki	=	340.0	nM	PMID[9379441]
NPT5167	Individual Protein	Endothelin receptor ET-A	Sus scrofa	IC50	=	7.5	nM	PMID[11738578]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	80.0	nM	DOI[10.1016/S0960-894X(97)00400-9]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	8.0	nM	DOI[10.1016/S0960-894X(97)00400-9]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	IC50	=	150.0	nM	DOI[10.1016/S0960-894X(97)00400-9]
NPT3951	Individual Protein	Endothelin receptor ET-A	Rattus norvegicus	Kd	=	50.12	nM	DOI[10.1016/S0960-894X(97)00400-9]
NPT5168	Individual Protein	Endothelin receptor ET-B	Rattus norvegicus	Kd	=	1584.89	nM	DOI[10.1016/S0960-894X(97)00400-9]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	40.0	nM	PMID[12617929]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	IC50	=	280.0	nM	PMID[12617929]
NPT3951	Individual Protein	Endothelin receptor ET-A	Rattus norvegicus	Kd	=	72.44	nM	PMID[12617929]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	Ki	=	8.0	nM	PMID[12502366]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	Ki	=	80.0	nM	PMID[12502366]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	8.9	nM	PMID[22750010]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	IC50	=	202.0	nM	PMID[22862294]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	45.0	nM	PMID[22862294]
NPT5168	Individual Protein	Endothelin receptor ET-B	Rattus norvegicus	IC50	=	95.0	nM	PMID[25614116]
NPT3951	Individual Protein	Endothelin receptor ET-A	Rattus norvegicus	IC50	=	4.7	nM	PMID[25614116]
NPT543	Individual Protein	Pregnane X receptor	Homo sapiens	EC50	=	14100.0	nM	PMID[20966043]
NPT543	Individual Protein	Pregnane X receptor	Homo sapiens	EC50	=	12600.0	nM	PMID[20966043]
NPT543	Individual Protein	Pregnane X receptor	Homo sapiens	EC50	=	8900.0	nM	PMID[20966043]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	8.4	nM	DOI[10.1039/C5MD00169B]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	4.7	nM	PMID[27318985]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	IC50	=	95.0	nM	PMID[27318985]
NPT1249	Individual Protein	Canalicular multispecific organic anion transporter 2	Homo sapiens	IC50	=	42000.0	nM	PMID[23956101]
NPT1028	Individual Protein	Multidrug resistance-associated protein 4	Homo sapiens	IC50	=	22000.0	nM	PMID[23956101]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	1584.89	nM	PMID[29939744]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	IC50	=	1000.0	nM	PMID[29939744]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	80.0	nM	PMID[27321813]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	IC50	=	150.0	nM	PMID[27321813]
NPT3951	Individual Protein	Endothelin receptor ET-A	Rattus norvegicus	Kd	=	39.81	nM	PMID[27321813]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	45.0	nM	PMID[27321813]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	IC50	=	202.0	nM	PMID[27321813]
NPT247	Individual Protein	Endothelin receptor ET-A	Homo sapiens	IC50	=	45.0	nM	PMID[27266371]
NPT3952	Individual Protein	Endothelin receptor ET-B	Homo sapiens	IC50	=	202.0	nM	PMID[27266371]
NPT109	Individual Protein	Cytochrome P450 3A4	Homo sapiens	FC	=	1.0	n.a.	PMID[27397500]
NPT110	Individual Protein	Cytochrome P450 2D6	Homo sapiens	FC	=	1.0	n.a.	PMID[27397500]
NPT212	Individual Protein	Cytochrome P450 2C9	Homo sapiens	FC	=	1.0	n.a.	PMID[27397500]
NPT2	Others	Unspecified		Ratio	=	53.0	n.a.	PMID[9379441]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	Kb	=	130.0	nM	PMID[12502366]
NPT18446	SINGLE PROTEIN	Endothelin receptor type A	Oryctolagus cuniculus	Inhibition	=	22.54	%	PMID[21652209]
NPT712	Individual Protein	Bile salt export pump	Rattus norvegicus	Ki	=	12000.0	nM	PMID[11309550]
NPT2	Others	Unspecified		Ratio IC50	=	20.0	n.a.	PMID[25614116]
NPT712	Individual Protein	Bile salt export pump	Rattus norvegicus	IC50	=	30600.0	nM	PMID[21965623]
NPT713	Individual Protein	Bile salt export pump	Homo sapiens	IC50	=	38100.0	nM	PMID[21965623]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	195900.0	nM	PMID[27318985]
NPT713	Individual Protein	Bile salt export pump	Homo sapiens	IC50	=	22000.0	nM	PMID[20829430]
NPT713	Individual Protein	Bile salt export pump	Homo sapiens	IC50	=	29000.0	nM	PMID[24799086]
NPT1593	Tissue	Liver	Rattus norvegicus	IC50	>	100.0	nM	PMID[24799086]
NPT713	Individual Protein	Bile salt export pump	Homo sapiens	IC50	<	25300.0	nM	PMID[22961681]
NPT713	Individual Protein	Bile salt export pump	Homo sapiens	IC50	=	23000.0	nM	PMID[23956101]
NPT2	Others	Unspecified		Ratio	=	0.059	n.a.	PMID[23956101]
NPT2	Others	Unspecified		Ratio	=	0.032	n.a.	PMID[23956101]
NPT2	Others	Unspecified		Ratio	=	0.061	n.a.	PMID[23956101]
NPT2	Others	Unspecified		EC50	=	530.0	nM	PMID[28720331]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.48	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT748	Individual Protein	Bile acid transporter	Homo sapiens	IC50	=	30000000.0	nM	PMID[31439379]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	12.14	%	DOI[10.6019/CHEMBL4495564]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	4.397	%	DOI[10.6019/CHEMBL4495564]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.51	%	DOI[10.6019/CHEMBL4495565]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.24	%	DOI[10.6019/CHEMBL4495565]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	20000.0	nM	DOI[10.6019/CHEMBL4651402]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	19952.62	nM	DOI[10.6019/CHEMBL4651402]
NPT27	Others	Unspecified		Ratio	=	0.69	n.a.	PMID[32985885]
NPT27	Others	Unspecified		Ratio	=	1.19	n.a.	PMID[32985885]
NPT27	Others	Unspecified		Ratio	=	0.668	n.a.	PMID[32985885]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC489650 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	599
0.1-0.2	5135
0.2-0.3	12645
0.3-0.4	12648
0.4-0.5	10166
0.5-0.6	1424
0.6-0.7	79
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC489650 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	277
0.1-0.2	746
0.2-0.3	886
0.3-0.4	2287
0.4-0.5	3007
0.5-0.6	1536
0.6-0.7	388
0.7-0.8	17
0.8-0.85	2
0.85-0.9	2
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data