NPASS Compound

Natural Product: NPC194839

Natural Product ID	NPC194839
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BRYKANSBPAKIAC-DQIAKBPPSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	24762751
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 67 71 0 0 0 0 0 0 0 0999 V2000 -1.9186 1.5522 -2.7211 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0150 0.7777 -2.0436 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1710 1.4019 -0.6319 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8342 1.6044 -0.0426 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7255 2.8981 0.2851 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5436 3.3624 0.7922 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5487 2.5021 0.9674 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4712 1.1680 0.6382 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7325 0.7560 0.1448 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5715 -0.6832 -0.0377 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8621 -1.5660 -1.1048 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5192 -2.8672 -0.9818 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1037 -3.2998 0.1844 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3772 -2.4052 1.2322 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0320 -1.0790 1.1205 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2403 -0.1537 2.1035 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6744 0.1162 3.1495 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9905 -3.1715 2.2206 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9611 -4.5342 1.9155 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5546 -4.5552 0.5629 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5846 -1.3216 -2.3787 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9014 -0.6752 -2.0627 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9329 -1.2874 -3.0285 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7846 -0.6659 -3.2571 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4840 0.2689 0.7484 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3951 -0.0369 -0.2438 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1902 0.6030 -1.3022 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4758 -0.9872 -0.0961 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3512 -1.2910 -1.1193 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3786 -2.1937 -0.9296 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5686 -2.8235 0.2825 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6924 -2.5211 1.3101 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6722 -1.6206 1.1131 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6898 3.0538 1.4790 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8600 3.0637 2.8855 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4344 4.6989 1.1335 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5436 5.5441 0.9512 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9509 1.4942 -2.2165 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2314 2.6324 -2.6780 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8698 1.3246 -3.8164 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9683 1.0840 -2.5565 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7403 2.3292 -0.6768 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7690 0.6610 -0.0400 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5510 3.5717 0.1552 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7446 -3.5440 -1.8126 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1716 0.4584 4.0793 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2447 -0.8373 3.2966 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3454 0.9241 2.8245 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9652 -4.9779 2.0707 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1952 -4.9994 2.5832 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7859 -2.3467 -2.8031 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2122 -1.0788 -1.0604 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5895 -1.1250 -4.0650 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9439 -0.9090 -2.8280 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9077 -2.3804 -2.8410 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9110 -0.9856 -4.2017 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2232 -0.8070 -2.0828 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0841 -2.4450 -1.7332 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3588 -3.5360 0.4737 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7818 -2.9817 2.2932 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9997 -1.3855 1.9222 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2150 3.7924 3.3982 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5243 2.0572 3.2529 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9246 3.1506 3.1761 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9058 5.5339 -0.1083 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3817 5.0991 1.5450 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3355 6.5940 1.2110 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 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 1 0 14 18 1 0 18 19 1 0 19 20 1 0 11 21 1 0 21 22 1 0 22 23 1 0 21 24 1 0 8 25 1 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 7 34 1 0 34 35 1 0 6 36 1 0 36 37 1 0 22 2 1 0 33 28 1 0 9 4 1 0 15 10 1 0 20 13 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 6 3 42 1 0 3 43 1 0 5 44 1 0 12 45 1 0 17 46 1 0 17 47 1 0 17 48 1 0 19 49 1 0 19 50 1 0 21 51 1 6 22 52 1 1 23 53 1 0 23 54 1 0 23 55 1 0 24 56 1 0 29 57 1 0 30 58 1 0 31 59 1 0 32 60 1 0 33 61 1 0 35 62 1 0 35 63 1 0 35 64 1 0 37 65 1 0 37 66 1 0 37 67 1 0 M END

Standard InCHIKey	BRYKANSBPAKIAC-DQIAKBPPSA-N
Standard InCHI	InChI=1S/C29H30O8/c1-15-11-18-12-20(32-3)25(33-4)28(37-29(31)17-9-7-6-8-10-17)22(18)23-19(24(30)16(15)2)13-21-26(27(23)34-5)36-14-35-21/h6-10,12-13,15-16,24,30H,11,14H2,1-5H3/t15-,16-,24-/m1/s1
SMILES	C[C@@H]1Cc2cc(c(c(c2-c2c(cc3c(c2OC)OCO3)[C@@H]([C@@H]1C)O)OC(=O)c1ccccc1)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	506.19	Volume:	511.315 ? Van der Waals volume.
Dense:	0.99	LogP:	4.573 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.798 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.533 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	29.0
TPSA:	92.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.373	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.755	Fsp³:	0.345
MCE-18:	97.692 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.96	Fluc inhibitor:	0.033 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.636 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.736 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.023	Promiscuous compounds:	0.073

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.015	MDCK Permeability:	-4.695
Pgp-inhibitor:	0.888	Pgp-substrate:	0.006
PAMPA:	0.059 ? 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%):	0.01	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.484

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.284	MRP1:	0.973
Plasma Protein Binding (PPB):	98.554%	Volume Distribution (VD):	0.144
Fu:	1.371% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.986
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.004
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.348	CYP1A2-substrate:	0.541
CYP2C19-inhibitor:	0.561	CYP2C19-substrate:	0.5
CYP2C9-inhibitor:	0.442	CYP2C9-substrate:	0.192
CYP2D6-inhibitor:	0.022	CYP2D6-substrate:	0.615
CYP3A4-inhibitor:	0.096	CYP3A4-substrate:	0.973
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.237
HLM stability:	0.715 ? 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):

3.597

Half-life (T1/2):

0.966

ADMET: Toxicity

hERG Blockers:	0.203	hERG Blockers (10um):	0.786
Human Hepatotoxicity (H-HT):	0.212	Drug-induced Liver Injury (DILI):	0.789
AMES Toxicity:	0.448	Rat Oral Acute Toxicity:	0.46
Maximum Recommended Daily Dose:	0.48	Skin Sensitization:	0.85
Carcinogencity:	0.899	Eye Corrosion:	0.0
Eye Irritation:	0.202	Respiratory Toxicity:	0.68
Drug-induced Neurotoxicity:	0.757	Ototoxicity:	0.352
Hematotoxicity:	0.341	Drug-induced Nephrotoxicity:	0.38
Genotoxicity:	0.514	RPMI-8226 Immunitoxicity:	0.178
A549 Cytotoxicity:	0.821	Hek293 Cytotoxicity:	0.737
BCF:	1.316 ? 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:	4.205 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.382 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.884 ? 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
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18027905]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18271558]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	roots	n.a.	n.a.	PMID[18491866]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18590312]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24299567]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26214125]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	Stems	n.a.	n.a.	PMID[27704807]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34684838]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO912	Kadsura coccinea	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO912	Kadsura coccinea	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

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 NPC194839 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	16464
0.1-0.2	31074
0.2-0.3	2110
0.3-0.4	128
0.4-0.5	43
0.5-0.6	28
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.871	High Similarity	NPC249070
0.7742	Intermediate Similarity	NPC230538
0.7742	Intermediate Similarity	NPC229172
0.7742	Intermediate Similarity	NPC103637
0.7742	Intermediate Similarity	NPC36531
0.7419	Intermediate Similarity	NPC172171
0.7419	Intermediate Similarity	NPC239254
0.6901	Remote Similarity	NPC473323
0.6806	Remote Similarity	NPC473425
0.6197	Remote Similarity	NPC166506
0.6197	Remote Similarity	NPC110763
0.6032	Remote Similarity	NPC324962
0.5915	Remote Similarity	NPC328122
0.589	Remote Similarity	NPC189239
0.5775	Remote Similarity	NPC477381
0.5714	Remote Similarity	NPC145722
0.5714	Remote Similarity	NPC475868
0.5714	Remote Similarity	NPC256776
0.5714	Remote Similarity	NPC185680
0.5694	Remote Similarity	NPC477879
0.5526	Remote Similarity	NPC191352
0.55	Remote Similarity	NPC83049
0.55	Remote Similarity	NPC320471
0.55	Remote Similarity	NPC118162
0.5455	Remote Similarity	NPC471180
0.5429	Remote Similarity	NPC46277
0.5397	Remote Similarity	NPC32189
0.5375	Remote Similarity	NPC280778
0.5375	Remote Similarity	NPC471181
0.5278	Remote Similarity	NPC304821
0.5278	Remote Similarity	NPC301765
0.525	Remote Similarity	NPC79322
0.52	Remote Similarity	NPC325720
0.52	Remote Similarity	NPC316676
0.5139	Remote Similarity	NPC220577
0.5139	Remote Similarity	NPC475865
0.5125	Remote Similarity	NPC258322
0.507	Remote Similarity	NPC53722
0.507	Remote Similarity	NPC201404
0.507	Remote Similarity	NPC290714

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC194839 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2626
0.1-0.2	6357
0.2-0.3	167
0.3-0.4	0
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