NPASS Compound

Natural Product: NPC96566

Natural Product ID	NPC96566
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	WDUKPMSWWVPFRK-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	24795708
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002586] O-methylated isoflavonoids [CHEMONTID:0002606] 4'-O-methylated isoflavonoids [CHEMONTID:0002687] 4'-O-methylisoflavones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 46 48 0 0 0 0 0 0 0 0999 V2000 5.8964 -0.7443 1.2506 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8280 0.3291 1.1090 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5721 -0.0267 1.2664 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4813 0.9315 1.1477 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4699 0.5646 0.1226 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2465 0.0305 0.5097 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6722 -0.3051 -0.4676 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9665 -0.8714 -0.1134 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1618 -2.2286 0.0047 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3257 -2.7511 0.3247 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3971 -2.0282 0.5582 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6008 -2.5980 0.8908 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6807 -1.7872 1.1223 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5879 -0.3999 1.0286 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3757 0.1380 0.6954 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2678 -0.6332 0.4550 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0583 -0.0626 0.1211 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0038 1.1890 0.0440 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9199 -2.3083 1.4617 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3409 -0.0969 -1.7967 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8702 0.4322 -2.1868 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7960 0.7700 -1.1988 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0197 1.3035 -1.5703 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3124 1.4970 -2.9388 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2961 -0.4481 -2.7559 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3085 1.7068 0.8110 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6079 -1.3213 2.1512 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8640 -0.2863 1.4399 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9452 -1.3481 0.3399 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3279 -1.0589 1.4907 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0130 1.0352 2.1548 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8943 1.9320 0.9130 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0484 -0.1069 1.5638 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3500 -2.9204 -0.1650 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6937 -3.6565 0.9685 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4516 0.2283 1.2150 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2460 1.2270 0.6079 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7607 -1.7483 1.5030 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0707 0.5708 -3.2402 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5216 2.1244 -3.4415 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2596 2.0509 -3.0903 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3981 0.5523 -3.5045 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0928 0.1253 -2.9734 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3428 1.9226 -0.2895 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7595 2.4988 1.3454 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3962 1.7846 1.1162 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 13 19 1 0 7 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 20 25 1 0 2 26 1 0 22 5 1 0 17 8 1 0 16 11 1 0 1 27 1 0 1 28 1 0 1 29 1 0 3 30 1 0 4 31 1 0 4 32 1 0 6 33 1 0 9 34 1 0 12 35 1 0 14 36 1 0 15 37 1 0 19 38 1 0 21 39 1 0 24 40 1 0 24 41 1 0 24 42 1 0 25 43 1 0 26 44 1 0 26 45 1 0 26 46 1 0 M END

Standard InCHIKey	WDUKPMSWWVPFRK-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H20O5/c1-12(2)4-5-13-8-16(18(23)10-19(13)25-3)17-11-26-20-9-14(22)6-7-15(20)21(17)24/h4,6-11,22-23H,5H2,1-3H3
SMILES	CC(=CCc1cc(c2coc3cc(ccc3c2=O)O)c(cc1OC)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	352.13	Volume:	366.326 ? Van der Waals volume.
Dense:	0.961	LogP:	3.81 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.299 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.865 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	19.0
TPSA:	79.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.681	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.67	Fsp³:	0.19
MCE-18:	19.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.85	Fluc inhibitor:	0.694 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.895 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.572 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.332	Promiscuous compounds:	0.062

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.765	MDCK Permeability:	-4.688
Pgp-inhibitor:	0.022	Pgp-substrate:	0.093
PAMPA:	0.27 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.031
20% Bioavailability (F20%):	0.976	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.791
Plasma Protein Binding (PPB):	90.255%	Volume Distribution (VD):	0.259
Fu:	9.79% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.791
OATP1B3 inhibitor:	0.967	BCRP inhibitor:	0.993
BSEP inhibitor:	0.48

ADMET: Metabolism

CYP1A2-inhibitor:	0.239	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.682	CYP2C19-substrate:	0.945
CYP2C9-inhibitor:	0.225	CYP2C9-substrate:	0.862
CYP2D6-inhibitor:	0.767	CYP2D6-substrate:	0.902
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.979 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

7.636

Half-life (T1/2):

1.398

ADMET: Toxicity

hERG Blockers:	0.188	hERG Blockers (10um):	0.596
Human Hepatotoxicity (H-HT):	0.584	Drug-induced Liver Injury (DILI):	0.645
AMES Toxicity:	0.646	Rat Oral Acute Toxicity:	0.772
Maximum Recommended Daily Dose:	0.849	Skin Sensitization:	0.488
Carcinogencity:	0.741	Eye Corrosion:	0.001
Eye Irritation:	0.878	Respiratory Toxicity:	0.877
Drug-induced Neurotoxicity:	0.451	Ototoxicity:	0.399
Hematotoxicity:	0.202	Drug-induced Nephrotoxicity:	0.355
Genotoxicity:	0.931	RPMI-8226 Immunitoxicity:	0.087
A549 Cytotoxicity:	0.376	Hek293 Cytotoxicity:	0.661
BCF:	1.645 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.596 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.716 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.283 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO27807	Calotropis procera	Species	Apocynaceae	Eukaryota	root barks	n.a.	n.a.	PMID[15689169]
NPO27459	Balanophora tobiracola	Species	Balanophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27807	Calotropis procera	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22444	Ceramium boydenii	Species	Ceramiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27807	Calotropis procera	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22444	Ceramium boydenii	Species	Ceramiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27807	Calotropis procera	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27459	Balanophora tobiracola	Species	Balanophoraceae	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	Organism Name	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

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC96566 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	22402
0.1-0.2	23192
0.2-0.3	3693
0.3-0.4	445
0.4-0.5	86
0.5-0.6	27
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7353	Intermediate Similarity	NPC149875
0.7246	Intermediate Similarity	NPC104555
0.6515	Remote Similarity	NPC156953
0.6438	Remote Similarity	NPC609101
0.6418	Remote Similarity	NPC291802
0.6377	Remote Similarity	NPC161124
0.6269	Remote Similarity	NPC12175
0.6056	Remote Similarity	NPC215311
0.5797	Remote Similarity	NPC40290
0.5797	Remote Similarity	NPC195763
0.5692	Remote Similarity	NPC235428
0.5588	Remote Similarity	NPC203747
0.5588	Remote Similarity	NPC209560
0.5588	Remote Similarity	NPC490700
0.5588	Remote Similarity	NPC609386
0.5571	Remote Similarity	NPC191741
0.5526	Remote Similarity	NPC266572
0.5513	Remote Similarity	NPC7989
0.5467	Remote Similarity	NPC233918
0.5429	Remote Similarity	NPC262623
0.5429	Remote Similarity	NPC12377
0.5352	Remote Similarity	NPC80710
0.5352	Remote Similarity	NPC139364
0.5325	Remote Similarity	NPC26051
0.5325	Remote Similarity	NPC253822
0.5278	Remote Similarity	NPC200060
0.5278	Remote Similarity	NPC55162
0.5263	Remote Similarity	NPC268059
0.5263	Remote Similarity	NPC611071
0.5211	Remote Similarity	NPC121527
0.5195	Remote Similarity	NPC166036
0.5195	Remote Similarity	NPC128774
0.5185	Remote Similarity	NPC123653
0.5152	Remote Similarity	NPC212767
0.5067	Remote Similarity	NPC215375

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC96566 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3218
0.1-0.2	5835
0.2-0.3	91
0.3-0.4	6
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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