NPASS Compound

Natural Product: NPC308402

Natural Product ID	NPC308402
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GNXIIYFUGQWDJG-LAUBAEHRSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44257105
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003012] Flavan-3-ols [CHEMONTID:0001584] Catechins [CHEMONTID:0001587] Catechin gallates

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 50 53 0 0 0 0 0 0 0 0999 V2000 -1.1762 2.5968 -1.4583 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0177 3.1610 -1.9534 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1391 2.4378 -1.8648 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1496 1.1810 -1.2976 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0411 0.6364 -0.8048 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2029 1.3429 -0.8848 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4734 0.8162 -0.3839 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5580 0.8576 1.1351 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0151 0.6366 1.4817 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5325 -0.5466 0.7479 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7358 -1.0733 1.2268 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2457 -2.1728 0.5693 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6210 -2.7533 -0.5180 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4347 -2.2137 -0.9702 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8895 -1.1068 -0.3345 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6994 -0.5311 -0.7543 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1671 -3.8662 -1.1587 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3849 -0.5104 2.3169 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0856 2.0363 1.6638 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3517 0.4713 -1.2246 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1697 0.6085 -0.1094 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7558 1.3991 0.8040 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4359 -0.1000 0.0345 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1807 0.0864 1.1554 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3677 -0.5665 1.3097 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7983 -1.4063 0.3296 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0469 -1.5996 -0.8103 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8438 -0.9337 -0.9597 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5457 -2.4658 -1.7625 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0091 -2.0587 0.5104 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1045 -0.3467 2.4796 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3485 2.9663 -2.3542 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0856 3.1709 -1.5304 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0284 4.1409 -2.4068 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0373 -0.3344 -0.3658 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3571 1.4017 -0.7450 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9861 -0.0328 1.4921 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5720 1.5735 1.1907 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1296 0.4544 2.5866 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1867 -2.6142 0.9148 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8825 -2.6061 -1.8127 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1904 -3.8934 -1.2271 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0041 0.2721 2.1205 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6205 1.8358 2.5156 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8417 0.7632 1.9540 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2831 -1.1104 -1.8660 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1258 -2.5991 -2.6652 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7642 -1.5240 0.9519 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7459 0.4487 2.5266 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2963 3.6703 -3.0753 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 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 13 17 1 0 11 18 1 0 8 19 1 0 4 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 27 29 1 0 26 30 1 0 25 31 1 0 3 32 1 0 6 1 1 0 16 7 1 0 28 23 1 0 15 10 1 0 1 33 1 0 2 34 1 0 5 35 1 0 7 36 1 6 8 37 1 1 9 38 1 0 9 39 1 0 12 40 1 0 14 41 1 0 17 42 1 0 18 43 1 0 19 44 1 0 24 45 1 0 28 46 1 0 29 47 1 0 30 48 1 0 31 49 1 0 32 50 1 0 M END

Standard InCHIKey	GNXIIYFUGQWDJG-LAUBAEHRSA-N
Standard InCHI	InChI=1S/C22H18O10/c23-11-6-14(25)12-8-17(28)21(31-18(12)7-11)9-1-2-13(24)19(5-9)32-22(30)10-3-15(26)20(29)16(27)4-10/h1-7,17,21,23-29H,8H2/t17-,21+/m0/s1
SMILES	c1cc(c(cc1[C@@H]1[C@H](Cc2c(cc(cc2O1)O)O)O)OC(=O)c1cc(c(c(c1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	442.09	Volume:	416.38 ? Van der Waals volume.
Dense:	1.062	LogP:	1.488 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.586 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.478 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	177.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.181	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.586	Fsp³:	0.136
MCE-18:	84.24 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.803	Fluc inhibitor:	0.313 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.586 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.474 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.485	Promiscuous compounds:	0.637

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.729	MDCK Permeability:	-4.931
Pgp-inhibitor:	0.001	Pgp-substrate:	0.008
PAMPA:	0.844 ? 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):	0.0
20% Bioavailability (F20%):	0.926	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.998
Plasma Protein Binding (PPB):	93.666%	Volume Distribution (VD):	0.045
Fu:	6.886% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.783
OATP1B3 inhibitor:	0.959	BCRP inhibitor:	0.464
BSEP inhibitor:	0.034

ADMET: Metabolism

CYP1A2-inhibitor:	0.01	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.65
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.015
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.98
HLM stability:	0.0 ? 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):

8.688

Half-life (T1/2):

2.278

ADMET: Toxicity

hERG Blockers:	0.062	hERG Blockers (10um):	0.827
Human Hepatotoxicity (H-HT):	0.378	Drug-induced Liver Injury (DILI):	0.675
AMES Toxicity:	0.633	Rat Oral Acute Toxicity:	0.411
Maximum Recommended Daily Dose:	0.805	Skin Sensitization:	0.999
Carcinogencity:	0.259	Eye Corrosion:	0.001
Eye Irritation:	0.982	Respiratory Toxicity:	0.553
Drug-induced Neurotoxicity:	0.005	Ototoxicity:	0.791
Hematotoxicity:	0.011	Drug-induced Nephrotoxicity:	0.023
Genotoxicity:	0.986	RPMI-8226 Immunitoxicity:	0.011
A549 Cytotoxicity:	0.995	Hek293 Cytotoxicity:	0.659
BCF:	0.777 ? 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:	3.409 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.493 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.023 ? 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
NPO40956	Woodfordia uniflora	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[32639158]

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

Activity Type	# Activity
MIC	3

Activity Type	# Activity
Organism	3

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
NPT20	Organism	Candida albicans	Candida albicans	MIC	>	113100.0	nM	PMID[32639158]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	MIC	=	113100.0	nM	PMID[32639158]

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 NPC308402 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	22412
0.1-0.2	22836
0.2-0.3	4162
0.3-0.4	319
0.4-0.5	95
0.5-0.6	17
0.6-0.7	15
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
0.7937	Intermediate Similarity	NPC9636
0.7213	Intermediate Similarity	NPC16435
0.6406	Remote Similarity	NPC171932
0.6333	Remote Similarity	NPC268266
0.6333	Remote Similarity	NPC42760
0.6333	Remote Similarity	NPC220825
0.6333	Remote Similarity	NPC268342
0.6129	Remote Similarity	NPC261619
0.6129	Remote Similarity	NPC61477
0.6129	Remote Similarity	NPC78770
0.6129	Remote Similarity	NPC219876
0.6129	Remote Similarity	NPC126029
0.6129	Remote Similarity	NPC15658
0.6066	Remote Similarity	NPC207179
0.6066	Remote Similarity	NPC167571
0.6066	Remote Similarity	NPC278552
0.6	Remote Similarity	NPC289990
0.5846	Remote Similarity	NPC61946
0.5676	Remote Similarity	NPC28440
0.56	Remote Similarity	NPC603291
0.5556	Remote Similarity	NPC605048
0.5385	Remote Similarity	NPC47398
0.5385	Remote Similarity	NPC234333
0.5385	Remote Similarity	NPC260898
0.5132	Remote Similarity	NPC603842
0.507	Remote Similarity	NPC326037
0.507	Remote Similarity	NPC13858
0.5068	Remote Similarity	NPC38779
0.5068	Remote Similarity	NPC114179
0.5068	Remote Similarity	NPC68324
0.5068	Remote Similarity	NPC289322
0.5068	Remote Similarity	NPC156818
0.5068	Remote Similarity	NPC160512
0.506	Remote Similarity	NPC135021

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC308402 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4225
0.1-0.2	4836
0.2-0.3	78
0.3-0.4	4
0.4-0.5	4
0.5-0.6	1
0.6-0.7	2
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
0.6129	Remote Similarity	NPD1612	Clinical (unspecified phase)
0.6129	Remote Similarity	NPD1613	Phase 4
0.5114	Remote Similarity	NPD7993	Clinical (unspecified phase)

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