NPASS Compound

Natural Product: NPC473989

Natural Product ID	NPC473989
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Kadangustin B
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL457477
PubChem CID	24862636
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000238] Tannins [CHEMONTID:0001710] Hydrolyzable tannins

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 59 63 0 0 0 0 0 0 0 0999 V2000 2.8895 -0.3415 -2.4809 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5785 0.5225 -1.4084 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3617 1.1215 -1.2156 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9776 2.3380 -1.7152 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7179 3.2343 -2.4886 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0133 4.4844 -2.5067 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3192 4.1020 -2.1449 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2970 2.8801 -1.5007 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2146 2.1475 -0.7461 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8706 0.9394 -0.2323 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4224 0.4595 -0.4801 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1121 -0.7360 -0.0124 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7289 -2.0867 -0.0103 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6368 -3.0019 0.4045 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9012 -2.5785 0.8115 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2388 -1.2190 0.7990 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3311 -0.2777 0.3845 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5543 1.0799 0.3633 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3067 1.9182 1.4830 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5374 -1.0860 1.2476 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1487 -2.3631 1.2615 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0306 -3.2291 1.2751 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5565 -2.7838 -0.3023 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6202 -2.1314 0.6200 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3288 -1.0452 -0.0539 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0717 0.3756 0.4362 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1670 1.1410 -0.0171 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9629 1.7972 0.9017 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7129 1.7136 2.1428 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1362 2.6253 0.5187 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8525 -1.2268 0.0199 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9989 -1.7877 1.9447 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4157 -4.1248 -0.0268 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8567 -1.4085 -2.2196 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9201 -0.0972 -2.8113 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2214 -0.1724 -3.3468 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4737 5.1053 -1.7148 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0480 4.9612 -3.4911 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1866 2.5940 -0.6042 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3899 -4.0469 0.4219 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9257 1.3415 2.3472 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5259 2.6395 1.1860 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1962 2.5331 1.7332 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7897 -2.5225 2.1509 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6996 -2.5593 0.3160 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9021 -2.6577 -1.3271 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3408 -2.9731 0.8173 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0858 -1.0249 -1.1455 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0423 0.4441 1.5352 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4120 2.3357 -0.5170 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7919 3.6746 0.4994 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9993 2.4646 1.1903 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0586 -2.2966 0.2174 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2831 -0.6483 0.8487 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3303 -0.9310 -0.9329 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7493 -1.7726 2.7620 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2877 -2.6095 2.2120 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4494 -0.8533 1.9673 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0902 -4.3806 0.6336 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 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 16 17 2 0 17 18 1 0 18 19 1 0 16 20 1 0 20 21 1 0 21 22 1 0 13 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 28 30 1 0 25 31 1 0 24 32 1 0 23 33 1 0 11 3 1 0 17 12 1 0 8 4 1 0 26 10 1 0 22 15 1 0 1 34 1 0 1 35 1 0 1 36 1 0 6 37 1 0 6 38 1 0 9 39 1 0 14 40 1 0 19 41 1 0 19 42 1 0 19 43 1 0 21 44 1 0 21 45 1 0 23 46 1 6 24 47 1 1 25 48 1 6 26 49 1 1 30 50 1 0 30 51 1 0 30 52 1 0 31 53 1 0 31 54 1 0 31 55 1 0 32 56 1 0 32 57 1 0 32 58 1 0 33 59 1 0 M END

Standard InCHIKey	RUJHQOHNFCOAFM-VSBNPSRXSA-N
Standard InCHI	InChI=1S/C24H26O9/c1-10-11(2)20(33-12(3)25)14-7-16-22(32-9-30-16)24(28-5)18(14)17-13(19(10)26)6-15-21(23(17)27-4)31-8-29-15/h6-7,10-11,19-20,26H,8-9H2,1-5H3/t10-,11+,19-,20-/m0/s1
SMILES	COc1c2OCOc2cc2c1c1c(cc3c(c1OC)OCO3)[C@H]([C@H]([C@H]([C@@H]2OC(=O)C)C)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	458.16	Volume:	441.535 ? Van der Waals volume.
Dense:	1.038	LogP:	3.105 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.994 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.498 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	27.0
TPSA:	101.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.689	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.202	Fsp³:	0.458
MCE-18:	100.286 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.707	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.452 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.381 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.079	Promiscuous compounds:	0.289

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.044	MDCK Permeability:	-4.76
Pgp-inhibitor:	0.472	Pgp-substrate:	0.021
PAMPA:	0.602 ? 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):	0.001
20% Bioavailability (F20%):	0.085	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.623

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.556	MRP1:	0.98
Plasma Protein Binding (PPB):	93.759%	Volume Distribution (VD):	-0.502
Fu:	6.846% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.965
OATP1B3 inhibitor:	0.972	BCRP inhibitor:	0.004
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.992	CYP1A2-substrate:	0.859
CYP2C19-inhibitor:	0.928	CYP2C19-substrate:	0.324
CYP2C9-inhibitor:	0.582	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.613	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.012	CYP3A4-substrate:	0.791
CYP2B6-substrate:	0.376	CYP2C8-inhibitor:	0.001
HLM stability:	0.369 ? 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):

3.339

Half-life (T1/2):

1.273

ADMET: Toxicity

hERG Blockers:	0.118	hERG Blockers (10um):	0.375
Human Hepatotoxicity (H-HT):	0.71	Drug-induced Liver Injury (DILI):	0.957
AMES Toxicity:	0.935	Rat Oral Acute Toxicity:	0.547
Maximum Recommended Daily Dose:	0.825	Skin Sensitization:	0.829
Carcinogencity:	0.939	Eye Corrosion:	0.0
Eye Irritation:	0.33	Respiratory Toxicity:	0.724
Drug-induced Neurotoxicity:	0.748	Ototoxicity:	0.489
Hematotoxicity:	0.843	Drug-induced Nephrotoxicity:	0.858
Genotoxicity:	0.933	RPMI-8226 Immunitoxicity:	0.361
A549 Cytotoxicity:	0.621	Hek293 Cytotoxicity:	0.649
BCF:	1.093 ? 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:	3.295 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.965 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.025 ? 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
NPO18146	Kadsura angustifolia	Species	Schisandraceae	Eukaryota	stems	Honghe Prefecture of Yunnan Province, China	2005-Oct	PMID[18278869]
NPO18146	Kadsura angustifolia	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21232955]
NPO18146	Kadsura angustifolia	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18146	Kadsura angustifolia	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18146	Kadsura angustifolia	Species	Schisandraceae	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

Activity Type	# Activity
EC50	1
Ratio	1
CC50	1

Activity Type	# Activity
Cell line	1
Organism	1
Others	1

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
NPT1452	Cell line	C8166	Homo sapiens	CC50	>	200000.0	nM	PMID[19846302]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	149650.0	nM	PMID[23911853]
NPT2	Others	Unspecified	n.a.	Ratio	>	2.92	n.a.	PMID[23911853]

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 NPC473989 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	13096
0.1-0.2	34229
0.2-0.3	2253
0.3-0.4	173
0.4-0.5	63
0.5-0.6	22
0.6-0.7	15
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9615	High Similarity	NPC325720
0.9615	High Similarity	NPC316676
0.8421	Intermediate Similarity	NPC312763
0.8136	Intermediate Similarity	NPC24562
0.717	Intermediate Similarity	NPC326144
0.7059	Intermediate Similarity	NPC475868
0.6792	Remote Similarity	NPC324962
0.6667	Remote Similarity	NPC327651
0.6552	Remote Similarity	NPC318286
0.6349	Remote Similarity	NPC474054
0.6333	Remote Similarity	NPC321958
0.6333	Remote Similarity	NPC327352
0.6333	Remote Similarity	NPC198129
0.6333	Remote Similarity	NPC252281
0.6333	Remote Similarity	NPC321696
0.6167	Remote Similarity	NPC475865
0.6129	Remote Similarity	NPC76415
0.6129	Remote Similarity	NPC325122
0.6129	Remote Similarity	NPC218510
0.6	Remote Similarity	NPC172171
0.6	Remote Similarity	NPC239254
0.5926	Remote Similarity	NPC474295
0.5806	Remote Similarity	NPC230538
0.5806	Remote Similarity	NPC229172
0.5806	Remote Similarity	NPC103637
0.5806	Remote Similarity	NPC36531
0.5758	Remote Similarity	NPC319749
0.5714	Remote Similarity	NPC216434
0.5714	Remote Similarity	NPC103448
0.5714	Remote Similarity	NPC606558
0.5625	Remote Similarity	NPC322426
0.5588	Remote Similarity	NPC308739
0.5455	Remote Similarity	NPC316989
0.5429	Remote Similarity	NPC473323
0.5373	Remote Similarity	NPC85141
0.5362	Remote Similarity	NPC471154
0.5352	Remote Similarity	NPC473425
0.5211	Remote Similarity	NPC477380
0.5139	Remote Similarity	NPC477885
0.5072	Remote Similarity	NPC189239
0.507	Remote Similarity	NPC471180
0.5067	Remote Similarity	NPC63061
0.5067	Remote Similarity	NPC483405

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473989 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4421
0.1-0.2	4631
0.2-0.3	95
0.3-0.4	3
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