NPASS Compound

Natural Product: NPC2576

Natural Product ID	NPC2576
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LCSKDKPVRLILBJ-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44259765
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001615] Flavones [CHEMONTID:0001136] Flavonols

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 48 50 0 0 0 0 0 0 0 0999 V2000 -7.6125 0.3150 0.4056 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5094 -0.5268 -0.0685 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2856 -0.3851 0.4172 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0612 0.6554 1.4607 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1292 1.5785 1.0201 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8265 1.3551 0.7656 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0761 2.4349 0.2819 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7113 2.2693 0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0819 1.0903 0.1798 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8430 0.0332 0.6604 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1968 0.1715 0.9479 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3117 0.8551 -0.0902 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1614 1.8095 -0.5638 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4977 1.5040 -0.8002 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2295 2.4203 -1.2346 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9776 0.2512 -0.5634 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0561 -0.6729 -0.0810 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5573 -1.9357 0.1535 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8737 -2.2809 -0.0669 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7511 -1.3462 -0.5416 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2955 -0.0764 -0.7891 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1894 0.8711 -1.2714 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0700 -1.6420 -0.7766 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0872 -1.5031 0.1836 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3176 -3.5910 0.1947 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8173 -0.3630 0.1306 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7437 3.1235 -0.8329 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7702 -1.5502 -1.1061 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7349 0.1452 1.5038 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3760 1.3974 0.2767 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5778 0.0685 -0.1235 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4761 -1.0232 0.0430 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6851 0.0896 2.3733 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0227 1.1613 1.7348 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5231 3.3971 0.1192 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2396 3.1612 -0.3638 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3807 -0.9420 0.8231 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7059 -0.6819 1.3403 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8725 -2.6866 0.5301 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5935 1.5352 -0.6266 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6865 -1.2428 1.1731 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8518 -0.7905 -0.1799 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5742 -2.5134 0.2741 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6696 -4.2492 0.5818 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1493 3.8340 -0.2118 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4915 -1.1788 -2.1324 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1749 -2.4739 -0.9624 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8421 -1.8718 -1.1009 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 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 9 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 20 23 1 0 23 24 1 0 19 25 1 0 17 26 1 0 13 27 1 0 2 28 1 0 11 6 1 0 26 12 1 0 21 16 1 0 1 29 1 0 1 30 1 0 1 31 1 0 3 32 1 0 4 33 1 0 4 34 1 0 7 35 1 0 8 36 1 0 10 37 1 0 11 38 1 0 18 39 1 0 22 40 1 0 24 41 1 0 24 42 1 0 24 43 1 0 25 44 1 0 27 45 1 0 28 46 1 0 28 47 1 0 28 48 1 0 M END

Standard InCHIKey	LCSKDKPVRLILBJ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H20O7/c1-11(2)8-9-27-13-6-4-12(5-7-13)20-19(25)17(23)16-15(28-20)10-14(22)21(26-3)18(16)24/h4-8,10,22,24-25H,9H2,1-3H3
SMILES	CC(=CCOc1ccc(cc1)c1c(c(=O)c2c(cc(c(c2O)OC)O)o1)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	384.12	Volume:	383.906 ? Van der Waals volume.
Dense:	1.001	LogP:	3.955 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.069 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.776 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	19.0
TPSA:	109.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.572	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.679	Fsp³:	0.19
MCE-18:	20.0 ? 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:	0.862	Fluc inhibitor:	0.778 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.924 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.757 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.237	Promiscuous compounds:	0.184

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.136	MDCK Permeability:	-4.756
Pgp-inhibitor:	0.932	Pgp-substrate:	0.167
PAMPA:	0.289 ? 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):	0.08
20% Bioavailability (F20%):	0.061	30% Bioavailability (F30%):	0.595
50% Bioavailability (F50%):	0.923

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.015	MRP1:	0.96
Plasma Protein Binding (PPB):	98.017%	Volume Distribution (VD):	-0.744
Fu:	1.721% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.774
OATP1B3 inhibitor:	0.987	BCRP inhibitor:	0.974
BSEP inhibitor:	0.873

ADMET: Metabolism

CYP1A2-inhibitor:	0.969	CYP1A2-substrate:	0.574
CYP2C19-inhibitor:	0.076	CYP2C19-substrate:	0.918
CYP2C9-inhibitor:	0.926	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.991	CYP2D6-substrate:	0.225
CYP3A4-inhibitor:	0.049	CYP3A4-substrate:	0.031
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

4.639

Half-life (T1/2):

1.21

ADMET: Toxicity

hERG Blockers:	0.161	hERG Blockers (10um):	0.567
Human Hepatotoxicity (H-HT):	0.5	Drug-induced Liver Injury (DILI):	0.828
AMES Toxicity:	0.536	Rat Oral Acute Toxicity:	0.348
Maximum Recommended Daily Dose:	0.449	Skin Sensitization:	0.699
Carcinogencity:	0.706	Eye Corrosion:	0.071
Eye Irritation:	0.95	Respiratory Toxicity:	0.742
Drug-induced Neurotoxicity:	0.085	Ototoxicity:	0.247
Hematotoxicity:	0.268	Drug-induced Nephrotoxicity:	0.136
Genotoxicity:	0.406	RPMI-8226 Immunitoxicity:	0.066
A549 Cytotoxicity:	0.259	Hek293 Cytotoxicity:	0.379
BCF:	1.433 ? 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:	4.421 ? 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:	5.131 ? 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
NPO28296	Dryopteris dickinsii	Species	Dryopteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28277	Diospyros maingayi	Species	Ebenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28296	Dryopteris dickinsii	Species	Dryopteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27887	Striga asiatica	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28242	Amomum latifolium	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28277	Diospyros maingayi	Species	Ebenaceae	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 NPC2576 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	21301
0.1-0.2	25017
0.2-0.3	2841
0.3-0.4	585
0.4-0.5	89
0.5-0.6	17
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8	Intermediate Similarity	NPC44079
0.6897	Remote Similarity	NPC26227
0.6567	Remote Similarity	NPC213622
0.65	Remote Similarity	NPC98661
0.6176	Remote Similarity	NPC470402
0.6032	Remote Similarity	NPC49824
0.5873	Remote Similarity	NPC241838
0.5714	Remote Similarity	NPC203891
0.5714	Remote Similarity	NPC156222
0.5385	Remote Similarity	NPC201451
0.5373	Remote Similarity	NPC93376
0.5303	Remote Similarity	NPC256283
0.5224	Remote Similarity	NPC115798
0.5224	Remote Similarity	NPC200740
0.5224	Remote Similarity	NPC54394
0.5224	Remote Similarity	NPC255350
0.5211	Remote Similarity	NPC273538
0.5152	Remote Similarity	NPC276905
0.5152	Remote Similarity	NPC281207
0.5152	Remote Similarity	NPC605146
0.5075	Remote Similarity	NPC9609
0.5075	Remote Similarity	NPC86485
0.5068	Remote Similarity	NPC249824

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC2576 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4089
0.1-0.2	4932
0.2-0.3	123
0.3-0.4	4
0.4-0.5	0
0.5-0.6	2
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
0.5224	Remote Similarity	NPD2801	Pre-clinical
0.5211	Remote Similarity	NPD4378	Phase 3

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