NPASS Compound

Natural Product: NPC80078

Natural Product ID	NPC80078
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PLYBELSTMUBQBL-FCHUYYIVSA-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: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 53 56 0 0 0 0 0 0 0 0999 V2000 6.8721 2.4686 -0.1828 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2578 1.2024 0.2540 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4245 0.1249 0.4437 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0579 0.1681 0.2168 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2537 -0.9315 0.4176 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8489 -2.0896 0.8550 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2162 -2.1597 1.0900 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9931 -1.0557 0.8836 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3737 -1.1618 1.1314 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8053 -3.3448 1.5345 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8215 -0.9310 0.1931 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1549 -1.9730 0.3984 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1194 0.1838 -0.2482 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7335 0.1534 -0.4563 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1699 0.4602 0.5202 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5351 0.4235 0.2921 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9501 0.0613 -0.9720 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0455 -0.2552 -1.9812 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3074 -0.2084 -1.7200 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2290 -0.5244 -2.7260 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4860 -0.6181 -3.2497 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5136 0.7583 1.3573 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1168 -0.4483 2.0083 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2785 -1.0038 1.2905 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4469 -2.2382 1.2631 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2048 -0.1190 0.6299 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4357 -0.5287 0.1884 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3044 0.3363 -0.4407 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9018 1.6439 -0.6193 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6666 2.0494 -0.1747 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7774 1.2028 0.4587 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5468 1.6059 0.9018 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7512 2.5593 -1.2536 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7914 -1.8507 0.3920 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5906 -0.0324 3.2730 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7782 3.1364 -0.0891 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0864 2.8510 0.5128 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5533 2.4463 -1.2313 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6209 1.1005 -0.1288 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2940 -3.0107 1.0419 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0279 -1.3739 0.3906 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1589 -3.9889 0.8241 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1921 0.7379 1.4928 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9871 0.0083 -1.2312 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0015 0.1346 -2.8436 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9275 -0.2970 -4.0298 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9947 1.3314 2.1733 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3344 -1.2239 2.2218 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2739 0.0034 -0.7857 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4003 3.0798 -0.3383 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7534 2.4554 -1.0552 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9269 -2.1609 1.3445 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0709 0.8430 3.1215 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 7 10 1 0 5 11 1 0 11 12 2 0 11 13 1 0 13 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 18 21 1 0 16 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 29 33 1 0 27 34 1 0 23 35 1 0 8 3 1 0 19 14 1 0 32 22 1 0 31 26 1 0 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 6 40 1 0 9 41 1 0 10 42 1 0 15 43 1 0 17 44 1 0 20 45 1 0 21 46 1 0 22 47 1 1 23 48 1 1 28 49 1 0 30 50 1 0 33 51 1 0 34 52 1 0 35 53 1 0 M END

Standard InCHIKey	PLYBELSTMUBQBL-FCHUYYIVSA-N
Standard InCHI	InChI=1S/C23H18O12/c1-33-15-5-9(3-13(27)18(15)28)23(32)35-16-4-8(2-12(26)19(16)29)22-21(31)20(30)17-11(25)6-10(24)7-14(17)34-22/h2-7,21-22,24-29,31H,1H3/t21-,22+/m0/s1
SMILES	COc1cc(cc(c1O)O)C(=O)Oc1cc(cc(c1O)O)[C@@H]1[C@H](C(=O)c2c(cc(cc2O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	486.08	Volume:	448.62 ? Van der Waals volume.
Dense:	1.084	LogP:	1.222 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.262 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.134 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	25.0
TPSA:	203.44 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.16	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.688	Fsp³:	0.13
MCE-18:	88.308 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.838	Fluc inhibitor:	0.255 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.423 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.648 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.456	Promiscuous compounds:	0.696

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.583	MDCK Permeability:	-5.045
Pgp-inhibitor:	0.304	Pgp-substrate:	0.024
PAMPA:	0.827 ? 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):	0.046
20% Bioavailability (F20%):	0.764	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.983
Plasma Protein Binding (PPB):	96.563%	Volume Distribution (VD):	-0.434
Fu:	2.775% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.984
BSEP inhibitor:	0.036

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.074
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.004	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.049
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.825 ? 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):

7.042

Half-life (T1/2):

2.426

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.567
Human Hepatotoxicity (H-HT):	0.678	Drug-induced Liver Injury (DILI):	0.869
AMES Toxicity:	0.605	Rat Oral Acute Toxicity:	0.452
Maximum Recommended Daily Dose:	0.458	Skin Sensitization:	0.999
Carcinogencity:	0.19	Eye Corrosion:	0.001
Eye Irritation:	0.947	Respiratory Toxicity:	0.364
Drug-induced Neurotoxicity:	0.039	Ototoxicity:	0.61
Hematotoxicity:	0.098	Drug-induced Nephrotoxicity:	0.445
Genotoxicity:	0.95	RPMI-8226 Immunitoxicity:	0.081
A549 Cytotoxicity:	0.984	Hek293 Cytotoxicity:	0.62
BCF:	0.71 ? 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:	3.523 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.519 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.143 ? 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
NPO525	Actaea racemosa	Species	Ranunculaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[11824572]
NPO525	Actaea racemosa	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16124775]
NPO525	Actaea racemosa	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16562825]
NPO525	Actaea racemosa	Species	Ranunculaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[21082802]
NPO525	Actaea racemosa	Species	Ranunculaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[21082802]
NPO525	Actaea racemosa	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO525	Actaea racemosa	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO525	Actaea racemosa	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2403	Glochidion sumatranum	Species	Phyllanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2107	Leycesteria formosa	Species	Caprifoliaceae	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 NPC80078 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	25634
0.1-0.2	21023
0.2-0.3	2892
0.3-0.4	223
0.4-0.5	50
0.5-0.6	25
0.6-0.7	11
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
0.6364	Remote Similarity	NPC326037
0.6364	Remote Similarity	NPC13858
0.625	Remote Similarity	NPC36835
0.625	Remote Similarity	NPC246162
0.625	Remote Similarity	NPC9743
0.625	Remote Similarity	NPC260491
0.625	Remote Similarity	NPC61506
0.625	Remote Similarity	NPC240476
0.619	Remote Similarity	NPC19721
0.6061	Remote Similarity	NPC320825
0.6	Remote Similarity	NPC250922
0.5873	Remote Similarity	NPC21835
0.5846	Remote Similarity	NPC44721
0.5846	Remote Similarity	NPC211466
0.5846	Remote Similarity	NPC605332
0.5781	Remote Similarity	NPC62290
0.5781	Remote Similarity	NPC142731
0.5781	Remote Similarity	NPC326506
0.5538	Remote Similarity	NPC4152
0.5375	Remote Similarity	NPC36916
0.5375	Remote Similarity	NPC36
0.5375	Remote Similarity	NPC7154
0.5375	Remote Similarity	NPC125039
0.5375	Remote Similarity	NPC7688
0.5309	Remote Similarity	NPC138688
0.5309	Remote Similarity	NPC72787
0.5309	Remote Similarity	NPC217795
0.5309	Remote Similarity	NPC58223
0.5244	Remote Similarity	NPC279209
0.5244	Remote Similarity	NPC102277
0.5244	Remote Similarity	NPC479117
0.5147	Remote Similarity	NPC606962
0.5125	Remote Similarity	NPC606364
0.5075	Remote Similarity	NPC279417
0.5075	Remote Similarity	NPC208176
0.5075	Remote Similarity	NPC49130

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC80078 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5595
0.1-0.2	3523
0.2-0.3	22
0.3-0.4	4
0.4-0.5	3
0.5-0.6	3
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
0.5375	Remote Similarity	NPD6166	Phase 2
0.5375	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.5375	Remote Similarity	NPD6168	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