NPASS Compound

Natural Product: NPC533729

Natural Product ID	NPC533729
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[2-methoxy-5-[7-(3-methylbut-2-enoxy)-4-oxo-chromen-3-yl]phenyl] acetate
IUPAC Name	[2-methoxy-5-[7-(3-methylbut-2-enoxy)-4-oxo-chromen-3-yl]phenyl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 51 53 0 0 0 0 0 0 0 0999 V2000 -7.4383 1.4718 1.6799 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7249 0.3932 1.1223 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3934 0.5830 0.7790 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7625 1.7913 0.9705 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4443 1.9098 0.6087 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7153 0.8779 0.0610 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3083 1.0637 -0.3064 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9209 2.2136 -0.9959 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3175 2.4376 -1.3517 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2802 1.5863 -1.0791 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5808 1.8307 -1.4577 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6048 0.9171 -1.1634 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8446 1.2261 -1.5654 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0675 0.5897 -1.4542 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5284 0.3470 -0.0624 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7906 -0.8193 0.4707 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6823 -2.1189 -0.2020 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2455 -0.8420 1.9112 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2894 -0.2375 -0.4852 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9752 -0.4736 -0.1085 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9590 0.4180 -0.3924 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3343 0.1598 -0.0078 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6017 -0.8908 0.6057 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3778 -0.3152 -0.1161 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6960 -0.4725 0.2335 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3609 -1.7026 0.0454 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0216 -1.9485 -1.1602 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7427 -3.2414 -1.4071 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9822 -1.0403 -2.0208 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4354 1.1348 2.0630 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5895 2.2245 0.8991 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8809 1.9508 2.5350 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3241 2.6329 1.4071 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9477 2.8526 0.7568 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6860 2.9392 -1.2388 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8427 2.7310 -1.9896 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8676 1.1947 -1.9787 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0007 -0.3947 -2.0085 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6419 1.2783 0.5292 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7837 -2.0754 -1.2995 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4931 -2.7924 0.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7181 -2.6029 0.0942 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8621 -1.7605 2.1044 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3486 -0.9252 2.5528 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8393 0.0628 2.0802 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0143 -0.9850 -0.2255 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7211 -1.3688 0.4193 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8461 -1.1541 -0.5428 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1150 -3.5964 -0.4407 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0626 -4.0014 -1.8286 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5860 -3.0586 -2.1180 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 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 3 16 17 1 0 16 18 1 0 12 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 6 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 1 0 27 29 2 0 25 3 1 0 22 7 1 0 21 10 1 0 1 30 1 0 1 31 1 0 1 32 1 0 4 33 1 0 5 34 1 0 8 35 1 0 11 36 1 0 14 37 1 0 14 38 1 0 15 39 1 0 17 40 1 0 17 41 1 0 17 42 1 0 18 43 1 0 18 44 1 0 18 45 1 0 19 46 1 0 20 47 1 0 24 48 1 0 28 49 1 0 28 50 1 0 28 51 1 0 M END

Standard InCHIKey	QLKYJUBBIKGKSJ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C23H22O6/c1-14(2)9-10-27-17-6-7-18-21(12-17)28-13-19(23(18)25)16-5-8-20(26-4)22(11-16)29-15(3)24/h5-9,11-13H,10H2,1-4H3
SMILES	COC1=CC=C(C2=COC3=CC(OCC=C(C)C)=CC=C3C2=O)C=C1OC(C)=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	394.14	Volume:	407.072 ? Van der Waals volume.
Dense:	0.968	LogP:	3.813 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.402 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.076 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	20.0
TPSA:	74.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.342	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.449	Fsp³:	0.217
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:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.628	Fluc inhibitor:	0.835 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.951 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.511 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.329	Promiscuous compounds:	0.141

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.662	MDCK Permeability:	-4.511
Pgp-inhibitor:	0.854	Pgp-substrate:	0.113
PAMPA:	0.333 ? 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):	0.015
20% Bioavailability (F20%):	0.04	30% Bioavailability (F30%):	0.198
50% Bioavailability (F50%):	0.788

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.039	MRP1:	0.962
Plasma Protein Binding (PPB):	94.609%	Volume Distribution (VD):	-0.089
Fu:	4.685% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.387
BSEP inhibitor:	0.976

ADMET: Metabolism

CYP1A2-inhibitor:	0.777	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.008	CYP2C19-substrate:	0.746
CYP2C9-inhibitor:	0.975	CYP2C9-substrate:	0.323
CYP2D6-inhibitor:	0.951	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.41
CYP2B6-substrate:	0.005	CYP2C8-inhibitor:	0.999
HLM stability:	0.95 ? 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):

4.83

Half-life (T1/2):

0.55

ADMET: Toxicity

hERG Blockers:	0.197	hERG Blockers (10um):	0.524
Human Hepatotoxicity (H-HT):	0.564	Drug-induced Liver Injury (DILI):	0.936
AMES Toxicity:	0.574	Rat Oral Acute Toxicity:	0.498
Maximum Recommended Daily Dose:	0.473	Skin Sensitization:	0.633
Carcinogencity:	0.658	Eye Corrosion:	0.02
Eye Irritation:	0.785	Respiratory Toxicity:	0.671
Drug-induced Neurotoxicity:	0.406	Ototoxicity:	0.27
Hematotoxicity:	0.521	Drug-induced Nephrotoxicity:	0.239
Genotoxicity:	0.431	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.273	Hek293 Cytotoxicity:	0.258
BCF:	1.466 ? 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:	4.409 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.555 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.31 ? 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
NPO28288	Calopogonium mucunoides	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28288	Calopogonium mucunoides	Species	Fabaceae	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 NPC533729 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	28698
0.1-0.2	19429
0.2-0.3	1406
0.3-0.4	240
0.4-0.5	59
0.5-0.6	16
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9	High Similarity	NPC185401
0.7903	Intermediate Similarity	NPC254741
0.7049	Intermediate Similarity	NPC185607
0.6984	Remote Similarity	NPC471590
0.6667	Remote Similarity	NPC607700
0.6562	Remote Similarity	NPC136095
0.6389	Remote Similarity	NPC488570
0.6269	Remote Similarity	NPC602183
0.6184	Remote Similarity	NPC478528
0.6032	Remote Similarity	NPC182428
0.5823	Remote Similarity	NPC5840
0.5821	Remote Similarity	NPC186507
0.5775	Remote Similarity	NPC13967
0.5692	Remote Similarity	NPC195919
0.5672	Remote Similarity	NPC216314
0.56	Remote Similarity	NPC479305
0.5541	Remote Similarity	NPC249824
0.5541	Remote Similarity	NPC133400
0.5441	Remote Similarity	NPC479067
0.5362	Remote Similarity	NPC181124
0.527	Remote Similarity	NPC203636
0.5244	Remote Similarity	NPC189270
0.5211	Remote Similarity	NPC12377
0.5075	Remote Similarity	NPC120924
0.507	Remote Similarity	NPC148497
0.5068	Remote Similarity	NPC153008

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC533729 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4789
0.1-0.2	4241
0.2-0.3	117
0.3-0.4	2
0.4-0.5	0
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
0.5441	Remote Similarity	NPD2796	Phase 2

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