NPASS Compound

Natural Product: NPC256505

Natural Product ID	NPC256505
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YUPNHTWYVBHLMG-UPONEAKYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	49765092
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000048] Tetralins

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 26 27 0 0 0 0 0 0 0 0999 V2000 -2.8214 0.1734 0.6669 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8486 -0.1266 -0.4713 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3618 1.1731 -0.9989 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0056 1.5313 -0.6496 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3664 2.7334 -0.7707 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9585 0.5676 -0.1725 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5240 -0.6883 0.1174 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4412 -1.6189 0.5780 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7683 -1.2712 0.7371 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1963 0.0064 0.4395 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3001 0.9462 -0.0198 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6728 2.2468 -0.3353 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8597 -1.1091 -0.0314 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8445 -2.2389 -0.8896 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3182 -0.7598 0.9950 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5644 0.9220 0.2884 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2037 0.6378 1.4689 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4931 -0.5921 -1.2701 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0180 2.0196 -0.6741 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4264 1.1987 -2.1281 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1097 -2.6266 0.8140 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5186 -1.9740 1.0964 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2468 0.2836 0.5648 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4325 2.9653 0.3498 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1670 -1.5562 0.9626 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6141 -2.8436 -0.6673 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 4 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 7 13 1 0 13 14 1 0 13 2 1 0 11 6 1 0 1 15 1 0 1 16 1 0 1 17 1 0 2 18 1 6 3 19 1 0 3 20 1 0 8 21 1 0 9 22 1 0 10 23 1 0 12 24 1 0 13 25 1 1 14 26 1 0 M END

Standard InCHIKey	YUPNHTWYVBHLMG-UPONEAKYSA-N
Standard InCHI	InChI=1S/C11H12O3/c1-6-5-9(13)10-7(11(6)14)3-2-4-8(10)12/h2-4,6,11-12,14H,5H2,1H3/t6-,11+/m0/s1
SMILES	C[C@H]1CC(=O)c2c(cccc2O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	192.08	Volume:	197.524 ? Van der Waals volume.
Dense:	0.972	LogP:	1.033 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.191 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.194 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	12.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.657	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.256	Fsp³:	0.364
MCE-18:	40.8 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.287	Fluc inhibitor:	0.049 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.181 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.051 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.65	Promiscuous compounds:	0.321

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.814	MDCK Permeability:	-4.57
Pgp-inhibitor:	0.156	Pgp-substrate:	0.288
PAMPA:	0.977 ? 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):	0.018
20% Bioavailability (F20%):	0.176	30% Bioavailability (F30%):	0.462
50% Bioavailability (F50%):	0.842

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.062	MRP1:	0.797
Plasma Protein Binding (PPB):	42.582%	Volume Distribution (VD):	0.228
Fu:	55.593% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.143
BSEP inhibitor:	0.262

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.552	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.044
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.987	CYP3A4-substrate:	0.591
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.991 ? 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):

8.718

Half-life (T1/2):

1.163

ADMET: Toxicity

hERG Blockers:	0.039	hERG Blockers (10um):	0.367
Human Hepatotoxicity (H-HT):	0.691	Drug-induced Liver Injury (DILI):	0.459
AMES Toxicity:	0.848	Rat Oral Acute Toxicity:	0.559
Maximum Recommended Daily Dose:	0.268	Skin Sensitization:	0.966
Carcinogencity:	0.683	Eye Corrosion:	0.086
Eye Irritation:	0.932	Respiratory Toxicity:	0.835
Drug-induced Neurotoxicity:	0.474	Ototoxicity:	0.533
Hematotoxicity:	0.491	Drug-induced Nephrotoxicity:	0.72
Genotoxicity:	0.7	RPMI-8226 Immunitoxicity:	0.201
A549 Cytotoxicity:	0.649	Hek293 Cytotoxicity:	0.313
BCF:	0.769 ? 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:	3.186 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.464 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.648 ? 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
NPO26647	Ammannia baccifera	Species	Lythraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5057	Ephestia kuehniella	Species	Pyralidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27035	Artemisia eriopoda	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27167	Saguinus oedipus	Species	Cebidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26614	Planchonella duclitan	Species	Sapotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29101	Tanacetum larvatum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26647	Ammannia baccifera	Species	Lythraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13717	Aria elegans	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5057	Ephestia kuehniella	Species	Pyralidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25804	Vernonia zanzibarensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6591	Arthrospira maxima	Species	Microcoleaceae	Bacteria	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
IC50	1

Activity Type	# Activity
Cell line	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
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	>	520000.0	nM	PMID[34743062]

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 NPC256505 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	11851
0.1-0.2	33930
0.2-0.3	3849
0.3-0.4	195
0.4-0.5	24
0.5-0.6	7
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	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC234890
1.0	High Similarity	NPC74507
0.5745	Remote Similarity	NPC486434
0.5682	Remote Similarity	NPC247250
0.5682	Remote Similarity	NPC767
0.5581	Remote Similarity	NPC216297
0.5581	Remote Similarity	NPC473662
0.5581	Remote Similarity	NPC7151
0.5319	Remote Similarity	NPC601913

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC256505 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2949
0.1-0.2	5867
0.2-0.3	329
0.3-0.4	4
0.4-0.5	1
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