NPASS Compound

Natural Product: NPC243306

Natural Product ID	NPC243306
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FNUPUYFWZXZMIE-HUUCEWRRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	439493
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0001632] Flavanones [CHEMONTID:0001362] Flavanonols

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 33 35 0 0 0 0 0 0 0 0999 V2000 -2.9307 -0.8930 -0.8144 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0836 -0.2168 -0.4892 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0768 0.9225 0.3016 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8662 1.3743 0.7658 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7176 0.6930 0.4365 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7160 -0.4400 -0.3489 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4262 -1.1472 -0.6787 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0317 -1.9149 0.5430 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4347 -2.1506 0.5075 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9589 -3.2617 0.7630 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3178 -1.0429 0.1600 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6296 -0.9792 0.5936 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4435 0.0750 0.2534 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9132 1.0685 -0.5339 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6027 1.0353 -0.9854 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7979 -0.0385 -0.6302 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4907 -0.1483 -1.0345 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6608 2.1844 -0.9351 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3874 -1.1320 1.6609 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7950 2.5066 1.5598 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2702 1.5891 0.6150 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9482 -1.7960 -1.4427 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0517 -0.5531 -0.8431 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7457 1.0456 0.8022 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6165 -1.8666 -1.5085 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5999 -2.8544 0.6149 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9914 -1.7901 1.2106 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4625 0.1589 0.5695 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1811 1.8153 -1.6055 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7442 2.9954 -0.3350 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4354 -0.9647 2.2133 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2733 3.3332 1.2575 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5278 2.3926 0.0234 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 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 14 18 1 0 8 19 1 0 4 20 1 0 3 21 1 0 6 1 1 0 17 7 1 0 16 11 1 0 1 22 1 0 2 23 1 0 5 24 1 0 7 25 1 6 8 26 1 1 12 27 1 0 13 28 1 0 15 29 1 0 18 30 1 0 19 31 1 0 20 32 1 0 21 33 1 0 M END

Standard InCHIKey	FNUPUYFWZXZMIE-HUUCEWRRSA-N
Standard InCHI	InChI=1S/C15H12O6/c16-8-2-3-9-12(6-8)21-15(14(20)13(9)19)7-1-4-10(17)11(18)5-7/h1-6,14-18,20H/t14-,15-/m1/s1
SMILES	c1cc(c(cc1[C@@H]1[C@@H](C(=O)c2ccc(cc2O1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	288.06	Volume:	276.613 ? Van der Waals volume.
Dense:	1.041	LogP:	1.098 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.362 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.334 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.592	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.22	Fsp³:	0.133
MCE-18:	58.235 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.554	Fluc inhibitor:	0.627 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.214 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.141 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.604	Promiscuous compounds:	0.251

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.071	MDCK Permeability:	-4.861
Pgp-inhibitor:	0.002	Pgp-substrate:	0.061
PAMPA:	0.581 ? 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):	0.321
20% Bioavailability (F20%):	0.982	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.671
Plasma Protein Binding (PPB):	91.028%	Volume Distribution (VD):	-0.065
Fu:	15.008% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.945
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.215
BSEP inhibitor:	0.009

ADMET: Metabolism

CYP1A2-inhibitor:	0.84	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.977
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.871
HLM stability:	0.106 ? 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):

12.972

Half-life (T1/2):

2.427

ADMET: Toxicity

hERG Blockers:	0.105	hERG Blockers (10um):	0.636
Human Hepatotoxicity (H-HT):	0.573	Drug-induced Liver Injury (DILI):	0.546
AMES Toxicity:	0.692	Rat Oral Acute Toxicity:	0.584
Maximum Recommended Daily Dose:	0.362	Skin Sensitization:	0.999
Carcinogencity:	0.496	Eye Corrosion:	0.049
Eye Irritation:	0.982	Respiratory Toxicity:	0.591
Drug-induced Neurotoxicity:	0.168	Ototoxicity:	0.566
Hematotoxicity:	0.385	Drug-induced Nephrotoxicity:	0.236
Genotoxicity:	0.959	RPMI-8226 Immunitoxicity:	0.039
A549 Cytotoxicity:	0.937	Hek293 Cytotoxicity:	0.746
BCF:	1.268 ? 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:	3.579 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.566 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.213 ? 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
NPO4916	Toxicodendron vernicifluum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4916	Toxicodendron vernicifluum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4916	Toxicodendron vernicifluum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4916	Toxicodendron vernicifluum	Species	Anacardiaceae	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 NPC243306 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	20188
0.1-0.2	23914
0.2-0.3	4977
0.3-0.4	597
0.4-0.5	126
0.5-0.6	23
0.6-0.7	9
0.7-0.8	0
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC246328
1.0	High Similarity	NPC27532
0.8298	Intermediate Similarity	NPC325028
0.8298	Intermediate Similarity	NPC256346
0.8298	Intermediate Similarity	NPC606550
0.8222	Intermediate Similarity	NPC1940
0.75	Intermediate Similarity	NPC148011
0.7255	Intermediate Similarity	NPC36835
0.7255	Intermediate Similarity	NPC246162
0.7255	Intermediate Similarity	NPC9743
0.7255	Intermediate Similarity	NPC260491
0.7255	Intermediate Similarity	NPC61506
0.7255	Intermediate Similarity	NPC240476
0.7255	Intermediate Similarity	NPC609065
0.6981	Remote Similarity	NPC52530
0.6792	Remote Similarity	NPC611035
0.6667	Remote Similarity	NPC600246
0.64	Remote Similarity	NPC601844
0.6038	Remote Similarity	NPC1612
0.6038	Remote Similarity	NPC62290
0.6038	Remote Similarity	NPC142731
0.6038	Remote Similarity	NPC326506
0.6038	Remote Similarity	NPC183959
0.5926	Remote Similarity	NPC201837
0.5636	Remote Similarity	NPC19721
0.5536	Remote Similarity	NPC176869
0.5536	Remote Similarity	NPC3779
0.5455	Remote Similarity	NPC261619
0.5455	Remote Similarity	NPC61477
0.5455	Remote Similarity	NPC78770
0.5455	Remote Similarity	NPC219876
0.5455	Remote Similarity	NPC126029
0.5455	Remote Similarity	NPC15658
0.5441	Remote Similarity	NPC186847
0.5294	Remote Similarity	NPC150023
0.5273	Remote Similarity	NPC21835
0.5254	Remote Similarity	NPC320825
0.5217	Remote Similarity	NPC607309
0.5179	Remote Similarity	NPC279417
0.5179	Remote Similarity	NPC4152
0.5179	Remote Similarity	NPC49130
0.5161	Remote Similarity	NPC171651
0.5147	Remote Similarity	NPC163191
0.5082	Remote Similarity	NPC326037
0.5082	Remote Similarity	NPC13858
0.5082	Remote Similarity	NPC20907

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC243306 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3475
0.1-0.2	5464
0.2-0.3	196
0.3-0.4	7
0.4-0.5	5
0.5-0.6	2
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
0.5455	Remote Similarity	NPD1612	Clinical (unspecified phase)
0.5455	Remote Similarity	NPD1613	Phase 4

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