NPASS Compound

Natural Product: NPC265251

Natural Product ID	NPC265251
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CNMVOPXKKWCJHT-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	14839957
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0002817] Dibenzopyrans [CHEMONTID:0000200] Xanthenes [CHEMONTID:0000204] Xanthones

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 30 32 0 0 0 0 0 0 0 0999 V2000 5.3578 -0.0758 -0.2875 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1502 0.6274 -0.3805 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8991 0.0386 -0.1670 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7781 -1.2929 0.1535 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5274 -1.8219 0.3529 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3760 -1.0393 0.2378 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5451 0.2932 -0.0858 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8020 0.8675 -0.2962 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8839 2.2133 -0.6178 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5661 1.1009 -0.2092 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4340 2.3008 -0.4994 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7986 0.5269 -0.0003 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9197 1.3041 -0.1160 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1445 0.7274 0.0931 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2566 -0.6196 0.4167 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1299 -1.4070 0.5344 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8947 -0.8307 0.3248 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8157 -1.5632 0.4325 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5313 -1.1398 0.6154 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7739 2.6330 -0.4374 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1207 0.5130 -0.8648 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6886 -0.1226 0.7771 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3214 -1.1026 -0.6737 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6708 -1.8807 0.2383 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4017 -2.8533 0.6031 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6403 2.4472 -1.5891 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0759 1.3098 0.0119 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2565 -2.4510 0.7876 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7495 -2.0964 0.4207 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8162 3.3936 0.2247 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 10 11 2 0 10 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 15 19 1 0 13 20 1 0 8 3 1 0 17 12 1 0 18 6 1 0 1 21 1 0 1 22 1 0 1 23 1 0 4 24 1 0 5 25 1 0 9 26 1 0 14 27 1 0 16 28 1 0 19 29 1 0 20 30 1 0 M END

Standard InCHIKey	CNMVOPXKKWCJHT-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H10O6/c1-19-9-3-2-8-12(13(9)17)14(18)11-7(16)4-6(15)5-10(11)20-8/h2-5,15-17H,1H3
SMILES	COc1ccc2c(c1O)c(=O)c1c(cc(cc1o2)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	274.05	Volume:	259.317 ? Van der Waals volume.
Dense:	1.057	LogP:	2.159 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.239 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.957 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	17.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.587	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.45	Fsp³:	0.071
MCE-18:	18.0 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.46	Fluc inhibitor:	0.639 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.646 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.493 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.495	Promiscuous compounds:	0.852

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.177	MDCK Permeability:	-4.834
Pgp-inhibitor:	0.249	Pgp-substrate:	0.817
PAMPA:	0.091 ? 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):	0.022
20% Bioavailability (F20%):	0.147	30% Bioavailability (F30%):	0.797
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.037	MRP1:	0.75
Plasma Protein Binding (PPB):	97.341%	Volume Distribution (VD):	-0.675
Fu:	2.285% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.697
OATP1B3 inhibitor:	0.919	BCRP inhibitor:	0.969
BSEP inhibitor:	0.852

ADMET: Metabolism

CYP1A2-inhibitor:	0.967	CYP1A2-substrate:	0.495
CYP2C19-inhibitor:	0.009	CYP2C19-substrate:	0.083
CYP2C9-inhibitor:	0.926	CYP2C9-substrate:	0.085
CYP2D6-inhibitor:	0.995	CYP2D6-substrate:	0.57
CYP3A4-inhibitor:	0.03	CYP3A4-substrate:	0.012
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.957 ? 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):

2.565

Half-life (T1/2):

1.407

ADMET: Toxicity

hERG Blockers:	0.054	hERG Blockers (10um):	0.444
Human Hepatotoxicity (H-HT):	0.401	Drug-induced Liver Injury (DILI):	0.882
AMES Toxicity:	0.672	Rat Oral Acute Toxicity:	0.544
Maximum Recommended Daily Dose:	0.73	Skin Sensitization:	0.511
Carcinogencity:	0.835	Eye Corrosion:	0.472
Eye Irritation:	0.998	Respiratory Toxicity:	0.831
Drug-induced Neurotoxicity:	0.022	Ototoxicity:	0.061
Hematotoxicity:	0.077	Drug-induced Nephrotoxicity:	0.033
Genotoxicity:	0.919	RPMI-8226 Immunitoxicity:	0.065
A549 Cytotoxicity:	0.222	Hek293 Cytotoxicity:	0.569
BCF:	1.16 ? 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:	3.692 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.489 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.928 ? 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
NPO13329	Tephrosia polystachyoides	Species	Geometridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7994	Derris laxiflora	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15801	Hunteria umbellata	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8844	Stillingia sylvatica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8844	Stillingia sylvatica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8844	Stillingia sylvatica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23442	Cachonina hallii	Species	Heterocapsaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13329	Tephrosia polystachyoides	Species	Geometridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14940	Cedronella cana	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15801	Hunteria umbellata	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7994	Derris laxiflora	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16479	Tigridia pavonia	Species	Iridaceae	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
IC50	3

Activity Type	# Activity
Individual protein	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT497	Individual protein	Maltase-glucoamylase	Homo sapiens	IC50	=	71200.0	nM	PMID[30282319]
NPT497	Individual protein	Maltase-glucoamylase	Homo sapiens	IC50	=	71600.0	nM	PMID[30282319]

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 NPC265251 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	28949
0.1-0.2	17365
0.2-0.3	2893
0.3-0.4	537
0.4-0.5	98
0.5-0.6	10
0.6-0.7	6
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
0.6863	Remote Similarity	NPC14786
0.6863	Remote Similarity	NPC604806
0.68	Remote Similarity	NPC180234
0.6346	Remote Similarity	NPC101996
0.6038	Remote Similarity	NPC179183
0.6	Remote Similarity	NPC276930
0.5962	Remote Similarity	NPC610896
0.566	Remote Similarity	NPC603894
0.5385	Remote Similarity	NPC239495
0.5385	Remote Similarity	NPC169479
0.5385	Remote Similarity	NPC275734
0.5345	Remote Similarity	NPC487785
0.5192	Remote Similarity	NPC61620
0.5192	Remote Similarity	NPC194856
0.5185	Remote Similarity	NPC202157
0.5079	Remote Similarity	NPC241904

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC265251 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5174
0.1-0.2	3874
0.2-0.3	95
0.3-0.4	7
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