NPASS Compound

Natural Product: NPC114377

Natural Product ID	NPC114377
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DLUFCWQGHRQRMG-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5281945
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001615] Flavones [CHEMONTID:0003503] 6-prenylated flavones

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 43 45 0 0 0 0 0 0 0 0999 V2000 -5.1941 1.6147 0.1506 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9421 0.3300 -0.5425 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0885 -0.5506 -0.0471 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3872 -0.2264 1.2174 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9256 -0.1554 1.0976 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1739 0.1001 2.2399 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1989 0.1861 2.1943 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8614 0.0132 0.9730 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0839 -0.2400 -0.1459 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2962 -0.3270 -0.1041 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9494 -0.5825 -1.2888 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7239 -0.4120 -1.3518 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0728 -0.6461 -2.4084 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1255 -0.3190 -1.3696 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8478 -0.0667 -0.2389 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2763 0.0435 -0.1776 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8724 0.3099 1.0681 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2288 0.4339 1.2157 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0884 0.3050 0.1528 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5316 0.0455 -1.0699 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1406 -0.0835 -1.2323 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1507 0.0858 0.8831 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7025 -0.5029 -2.6169 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8139 0.2705 3.4413 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6514 0.0362 -1.8000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8671 2.2725 -0.4581 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6022 1.4062 1.1427 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2730 2.2155 0.3127 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9186 -1.5013 -0.5642 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7786 0.7130 1.6582 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6634 -1.0280 1.9378 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8014 0.3839 3.0733 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2741 0.1732 -1.8813 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2137 0.4183 1.9385 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6782 0.6392 2.1765 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1739 0.4070 0.2880 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1397 -0.0705 -1.9639 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7513 -0.2878 -2.2195 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5573 -1.3835 -3.1056 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0099 1.1820 3.8493 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2577 0.7335 -2.5936 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4070 -0.9698 -2.1357 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7477 0.2155 -1.6951 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 9 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 20 21 2 0 15 22 1 0 14 23 1 0 6 24 1 0 2 25 1 0 10 5 1 0 21 16 1 0 22 8 1 0 1 26 1 0 1 27 1 0 1 28 1 0 3 29 1 0 4 30 1 0 4 31 1 0 7 32 1 0 11 33 1 0 17 34 1 0 18 35 1 0 19 36 1 0 20 37 1 0 21 38 1 0 23 39 1 0 24 40 1 0 25 41 1 0 25 42 1 0 25 43 1 0 M END

Standard InCHIKey	DLUFCWQGHRQRMG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C20H18O5/c1-11(2)8-9-13-14(21)10-15-16(17(13)22)18(23)19(24)20(25-15)12-6-4-3-5-7-12/h3-8,10,21-22,24H,9H2,1-2H3
SMILES	CC(=CCc1c(cc2c(c1O)c(=O)c(c(c1ccccc1)o2)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	338.12	Volume:	349.03 ? Van der Waals volume.
Dense:	0.969	LogP:	4.39 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.308 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.538 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	19.0
TPSA:	90.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.626	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.621	Fsp³:	0.15
MCE-18:	19.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.912	Fluc inhibitor:	0.707 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.935 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.806 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.341	Promiscuous compounds:	0.091

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.018	MDCK Permeability:	-4.73
Pgp-inhibitor:	0.996	Pgp-substrate:	0.011
PAMPA:	0.378 ? 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):	0.056
20% Bioavailability (F20%):	0.085	30% Bioavailability (F30%):	0.858
50% Bioavailability (F50%):	0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.959
Plasma Protein Binding (PPB):	97.669%	Volume Distribution (VD):	-0.289
Fu:	2.005% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.976
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.971
BSEP inhibitor:	0.989

ADMET: Metabolism

CYP1A2-inhibitor:	0.017	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.511	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.989	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.993	CYP2D6-substrate:	0.03
CYP3A4-inhibitor:	0.053	CYP3A4-substrate:	0.997
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

3.994

Half-life (T1/2):

1.012

ADMET: Toxicity

hERG Blockers:	0.041	hERG Blockers (10um):	0.519
Human Hepatotoxicity (H-HT):	0.469	Drug-induced Liver Injury (DILI):	0.816
AMES Toxicity:	0.621	Rat Oral Acute Toxicity:	0.747
Maximum Recommended Daily Dose:	0.681	Skin Sensitization:	0.875
Carcinogencity:	0.561	Eye Corrosion:	0.031
Eye Irritation:	0.963	Respiratory Toxicity:	0.939
Drug-induced Neurotoxicity:	0.076	Ototoxicity:	0.142
Hematotoxicity:	0.109	Drug-induced Nephrotoxicity:	0.181
Genotoxicity:	0.951	RPMI-8226 Immunitoxicity:	0.065
A549 Cytotoxicity:	0.44	Hek293 Cytotoxicity:	0.6
BCF:	1.532 ? 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:	4.614 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.783 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.364 ? 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
NPO40192	Macaranga kurzii	Species	Euphorbiaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[23134335]
NPO40192	Macaranga kurzii	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
NPT91	Cell line	KB	Homo sapiens	IC50	=	10000.0	nM	PMID[23134335]

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 NPC114377 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	24381
0.1-0.2	22436
0.2-0.3	2529
0.3-0.4	394
0.4-0.5	78
0.5-0.6	31
0.6-0.7	3
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8364	Intermediate Similarity	NPC24821
0.8036	Intermediate Similarity	NPC157784
0.75	Intermediate Similarity	NPC270708
0.7213	Intermediate Similarity	NPC304295
0.6923	Remote Similarity	NPC212932
0.6667	Remote Similarity	NPC37684
0.6032	Remote Similarity	NPC284220
0.5938	Remote Similarity	NPC190637
0.5938	Remote Similarity	NPC3825
0.5672	Remote Similarity	NPC59210
0.5672	Remote Similarity	NPC269420
0.5672	Remote Similarity	NPC306488
0.5667	Remote Similarity	NPC473042
0.5522	Remote Similarity	NPC55018
0.5517	Remote Similarity	NPC187432
0.5441	Remote Similarity	NPC200694
0.5441	Remote Similarity	NPC14871
0.5417	Remote Similarity	NPC220418
0.541	Remote Similarity	NPC26227
0.541	Remote Similarity	NPC602367
0.5385	Remote Similarity	NPC9117
0.5366	Remote Similarity	NPC192587
0.5362	Remote Similarity	NPC65491
0.5362	Remote Similarity	NPC303633
0.5352	Remote Similarity	NPC602497
0.5342	Remote Similarity	NPC319752
0.5286	Remote Similarity	NPC488750
0.5254	Remote Similarity	NPC128216
0.5217	Remote Similarity	NPC189706
0.5205	Remote Similarity	NPC193200
0.5156	Remote Similarity	NPC603348
0.5152	Remote Similarity	NPC142339
0.5152	Remote Similarity	NPC63187
0.5079	Remote Similarity	NPC482122
0.5079	Remote Similarity	NPC152042
0.5075	Remote Similarity	NPC100123
0.5072	Remote Similarity	NPC273538
0.5072	Remote Similarity	NPC205046

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC114377 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3810
0.1-0.2	5244
0.2-0.3	92
0.3-0.4	2
0.4-0.5	1
0.5-0.6	1
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
0.5072	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