NPASS Compound

Natural Product: NPC97094

Natural Product ID	NPC97094
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NKPORGOKKIBGPG-GJZGRUSLSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
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:0001594] Epigallocatechins

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 38 40 0 0 0 0 0 0 0 0999 V2000 5.1097 1.7472 -0.8838 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4219 1.4814 0.3126 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2482 0.7233 0.3135 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3423 -0.6549 0.4654 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1893 -1.4322 0.4697 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9466 -0.8642 0.3259 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8738 0.4910 0.1778 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0021 1.2898 0.1695 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8677 2.6533 0.0164 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2411 -1.7498 0.3393 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8448 -1.7185 1.7251 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7900 -0.5766 1.8554 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8864 0.0977 2.9160 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6337 -0.2233 0.7213 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7768 0.5406 0.8475 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5650 0.8642 -0.2492 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2240 0.4261 -1.5125 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0806 -0.3364 -1.6294 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2823 -0.6675 -0.5379 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1446 -1.4297 -0.6746 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0024 0.7393 -2.6329 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1089 0.9762 2.1293 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1697 -1.6415 2.6779 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5812 -1.2607 0.6130 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3656 2.8229 -0.9351 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4283 1.5028 -1.7379 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0317 1.1313 -0.9779 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3190 -2.5042 0.5918 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0787 0.9780 0.0621 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4016 3.3133 0.5933 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0775 -2.8059 0.1668 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4555 -2.6450 1.8332 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4473 1.4580 -0.1277 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7903 -0.6936 -2.6128 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9109 0.2760 -2.7654 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8108 1.8614 2.5081 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7488 -2.4356 2.5441 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9490 -1.7344 -0.2141 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 6 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 17 21 1 0 15 22 1 0 11 23 1 0 4 24 1 0 8 3 1 0 20 10 1 0 19 14 1 0 1 25 1 0 1 26 1 0 1 27 1 0 5 28 1 0 7 29 1 0 9 30 1 0 10 31 1 6 11 32 1 1 16 33 1 0 18 34 1 0 21 35 1 0 22 36 1 0 23 37 1 0 24 38 1 0 M END

Standard InCHIKey	NKPORGOKKIBGPG-GJZGRUSLSA-N
Standard InCHI	InChI=1S/C16H14O8/c1-23-16-9(19)2-6(3-10(16)20)15-14(22)13(21)12-8(18)4-7(17)5-11(12)24-15/h2-5,14-15,17-20,22H,1H3/t14-,15-/m0/s1
SMILES	COc1c(cc(cc1O)[C@H]1[C@H](C(=O)c2c(cc(cc2O1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	334.07	Volume:	311.489 ? Van der Waals volume.
Dense:	1.072	LogP:	0.938 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.245 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.141 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	136.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.552	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.54	Fsp³:	0.188
MCE-18:	64.211 ? 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:	0
Colloidal aggregators:	0.635	Fluc inhibitor:	0.327 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.203 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.307 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.434	Promiscuous compounds:	0.398

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.86	MDCK Permeability:	-4.935
Pgp-inhibitor:	0.028	Pgp-substrate:	0.098
PAMPA:	0.587 ? 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):	0.039
20% Bioavailability (F20%):	0.585	30% Bioavailability (F30%):	0.977
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.011	MRP1:	0.899
Plasma Protein Binding (PPB):	96.098%	Volume Distribution (VD):	-0.563
Fu:	3.164% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.969
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.385
BSEP inhibitor:	0.005

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.03
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.101
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.021	CYP3A4-substrate:	0.893
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.28 ? 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):

6.211

Half-life (T1/2):

1.877

ADMET: Toxicity

hERG Blockers:	0.051	hERG Blockers (10um):	0.455
Human Hepatotoxicity (H-HT):	0.558	Drug-induced Liver Injury (DILI):	0.809
AMES Toxicity:	0.728	Rat Oral Acute Toxicity:	0.706
Maximum Recommended Daily Dose:	0.433	Skin Sensitization:	0.993
Carcinogencity:	0.521	Eye Corrosion:	0.005
Eye Irritation:	0.965	Respiratory Toxicity:	0.904
Drug-induced Neurotoxicity:	0.23	Ototoxicity:	0.398
Hematotoxicity:	0.633	Drug-induced Nephrotoxicity:	0.59
Genotoxicity:	0.975	RPMI-8226 Immunitoxicity:	0.283
A549 Cytotoxicity:	0.946	Hek293 Cytotoxicity:	0.862
BCF:	0.715 ? 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:	3.144 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.402 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.788 ? 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
NPO17698	Cirsium oligophyllum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16725	Dalbergia hupeana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16725	Dalbergia hupeana	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4591	Neobellieria bullata	Species	Sarcophagidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17698	Cirsium oligophyllum	Species	Asteraceae	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 NPC97094 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	25407
0.1-0.2	20231
0.2-0.3	3719
0.3-0.4	351
0.4-0.5	94
0.5-0.6	27
0.6-0.7	15
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC250922
0.8039	Intermediate Similarity	NPC320825
0.7917	Intermediate Similarity	NPC21835
0.78	Intermediate Similarity	NPC44721
0.78	Intermediate Similarity	NPC211466
0.78	Intermediate Similarity	NPC605332
0.76	Intermediate Similarity	NPC19721
0.7091	Intermediate Similarity	NPC326037
0.7091	Intermediate Similarity	NPC13858
0.7059	Intermediate Similarity	NPC62290
0.7059	Intermediate Similarity	NPC142731
0.7059	Intermediate Similarity	NPC326506
0.7059	Intermediate Similarity	NPC4152
0.6981	Remote Similarity	NPC36835
0.6981	Remote Similarity	NPC246162
0.6981	Remote Similarity	NPC9743
0.6981	Remote Similarity	NPC260491
0.6981	Remote Similarity	NPC61506
0.6981	Remote Similarity	NPC240476
0.6981	Remote Similarity	NPC609065
0.6481	Remote Similarity	NPC606962
0.6415	Remote Similarity	NPC47398
0.6415	Remote Similarity	NPC234333
0.6415	Remote Similarity	NPC279417
0.6415	Remote Similarity	NPC208176
0.6415	Remote Similarity	NPC260898
0.6415	Remote Similarity	NPC49130
0.6182	Remote Similarity	NPC306607
0.5857	Remote Similarity	NPC279209
0.5857	Remote Similarity	NPC102277
0.5857	Remote Similarity	NPC479117
0.5614	Remote Similarity	NPC176869
0.5614	Remote Similarity	NPC263449
0.5614	Remote Similarity	NPC3779
0.5571	Remote Similarity	NPC36916
0.5571	Remote Similarity	NPC36
0.5571	Remote Similarity	NPC7154
0.5571	Remote Similarity	NPC125039
0.5571	Remote Similarity	NPC7688
0.5507	Remote Similarity	NPC606364
0.5493	Remote Similarity	NPC138688
0.5493	Remote Similarity	NPC72787
0.5493	Remote Similarity	NPC217795
0.5493	Remote Similarity	NPC58223
0.5439	Remote Similarity	NPC122828
0.5429	Remote Similarity	NPC470326
0.5342	Remote Similarity	NPC75827
0.5333	Remote Similarity	NPC471515
0.5172	Remote Similarity	NPC325028
0.5172	Remote Similarity	NPC256346
0.5172	Remote Similarity	NPC606550
0.5167	Remote Similarity	NPC302950
0.5088	Remote Similarity	NPC476182
0.5085	Remote Similarity	NPC481903
0.5082	Remote Similarity	NPC52530

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC97094 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5550
0.1-0.2	3518
0.2-0.3	73
0.3-0.4	1
0.4-0.5	4
0.5-0.6	4
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
0.5571	Remote Similarity	NPD6166	Phase 2
0.5571	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.5571	Remote Similarity	NPD6168	Clinical (unspecified phase)
0.5167	Remote Similarity	NPD1934	Phase 0

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