NPASS Compound

Natural Product: NPC469675

Natural Product ID	NPC469675
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-[[(2R)-3,3-Dimethyloxiran-2-Yl]Methoxy]-8-[(2R,3R)-3-Prop-1-En-2-Yloxiran-2-Yl]Chromen-2-One
IUPAC Name	7-[[(2R)-3,3-dimethyloxiran-2-yl]methoxy]-8-[(2R,3R)-3-prop-1-en-2-yloxiran-2-yl]chromen-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1098139
PubChem CID	46831976
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives

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 44 47 0 0 0 0 0 0 0 0999 V2000 -3.3949 -2.9379 1.3116 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4361 -2.8011 0.1857 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7568 -3.8855 -0.1885 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2499 -1.4916 -0.4928 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8104 -0.3796 0.2740 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2718 -0.5440 -0.0562 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2675 0.8820 -0.2608 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0841 1.0252 -0.4901 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6207 2.2097 -0.9959 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2058 3.2753 -1.2797 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5596 3.1567 -1.0591 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0769 1.9616 -0.5521 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3626 1.8395 -0.3391 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2371 2.7791 -0.5703 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4539 2.5382 -0.3227 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7953 3.9782 -1.0690 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4555 4.1653 -1.3129 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8838 -0.0743 -0.1904 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2741 0.0534 -0.4190 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9657 -1.2366 -0.0350 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1010 -1.1316 0.9010 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8438 -1.6563 1.2795 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4616 0.1660 1.5488 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2310 -2.1328 0.7677 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6721 -3.9663 1.5293 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9238 -2.4751 2.2232 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3115 -2.3214 1.0767 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9169 -4.8143 0.3241 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0387 -3.8288 -1.0153 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1724 -1.5878 -1.5931 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7296 -0.4953 1.3754 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6876 2.2669 -1.1564 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1764 4.2162 -1.6757 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5284 4.7488 -1.2565 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1067 5.1085 -1.7054 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7092 0.9008 0.1714 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4713 0.2717 -1.4882 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0058 -2.0605 -0.7761 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6377 0.5319 2.2142 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7518 0.9402 0.8083 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3347 -0.0102 2.2088 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8619 -2.1908 1.6720 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8114 -3.1511 0.5474 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8206 -1.8422 -0.1188 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 5 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 2 0 8 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 21 24 1 0 6 4 1 0 12 7 2 0 17 11 1 0 22 20 1 0 1 25 1 0 1 26 1 0 1 27 1 0 3 28 1 0 3 29 1 0 4 30 1 0 5 31 1 0 9 32 1 0 10 33 1 0 16 34 1 0 17 35 1 0 19 36 1 0 19 37 1 0 20 38 1 0 23 39 1 0 23 40 1 0 23 41 1 0 24 42 1 0 24 43 1 0 24 44 1 0 M END

Standard InCHIKey	UGERORSNMILQIE-MZMPZRCHSA-N
Standard InCHI	InChI=1S/C19H20O5/c1-10(2)16-18(23-16)15-12(21-9-13-19(3,4)24-13)7-5-11-6-8-14(20)22-17(11)15/h5-8,13,16,18H,1,9H2,2-4H3/t13-,16-,18-/m1/s1
SMILES	CC(=C)C1C(O1)C2=C(C=CC3=C2OC(=O)C=C3)OCC4C(O4)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	328.13	Volume:	331.087 ? Van der Waals volume.
Dense:	0.991	LogP:	3.029 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.097 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.202 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	19.0
TPSA:	64.5 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.478	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.02	Fsp³:	0.421
MCE-18:	79.111 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.15	Fluc inhibitor:	0.012 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.992 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.289 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.298	Promiscuous compounds:	0.038

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.617	MDCK Permeability:	-4.443
Pgp-inhibitor:	0.003	Pgp-substrate:	0.0
PAMPA:	0.05 ? 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):	0.0
20% Bioavailability (F20%):	0.19	30% Bioavailability (F30%):	0.29
50% Bioavailability (F50%):	0.591

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.075	MRP1:	0.999
Plasma Protein Binding (PPB):	95.455%	Volume Distribution (VD):	0.129
Fu:	3.775% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.893
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.152	CYP1A2-substrate:	0.962
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.356
CYP2C9-inhibitor:	0.3	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.239	CYP2D6-substrate:	0.979
CYP3A4-inhibitor:	0.839	CYP3A4-substrate:	0.073
CYP2B6-substrate:	0.98	CYP2C8-inhibitor:	0.073
HLM stability:	0.978 ? 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):

9.26

Half-life (T1/2):

1.052

ADMET: Toxicity

hERG Blockers:	0.142	hERG Blockers (10um):	0.399
Human Hepatotoxicity (H-HT):	0.591	Drug-induced Liver Injury (DILI):	0.933
AMES Toxicity:	0.828	Rat Oral Acute Toxicity:	0.568
Maximum Recommended Daily Dose:	0.65	Skin Sensitization:	0.529
Carcinogencity:	0.742	Eye Corrosion:	0.015
Eye Irritation:	0.872	Respiratory Toxicity:	0.508
Drug-induced Neurotoxicity:	0.474	Ototoxicity:	0.3
Hematotoxicity:	0.324	Drug-induced Nephrotoxicity:	0.165
Genotoxicity:	0.932	RPMI-8226 Immunitoxicity:	0.1
A549 Cytotoxicity:	0.047	Hek293 Cytotoxicity:	0.376
BCF:	1.631 ? 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:	4.36 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.189 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.669 ? 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
NPO5744	Galipea panamensis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20423106]
NPO5744	Galipea panamensis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5744	Galipea panamensis	Species	Rutaceae	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
EC50	1
CC50	1

Activity Type	# Activity
Cell line	1
Organism	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
NPT466	Cell line	U-937	Homo sapiens	CC50	=	9.7	ug.mL-1	DOI[10.6019/CHEMBL1201861]
NPT3632	Organism	Leishmania panamensis	Leishmania panamensis	EC50	=	10.0	ug.mL-1	PMID[20547808]

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 NPC469675 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	18686
0.1-0.2	30356
0.2-0.3	562
0.3-0.4	165
0.4-0.5	53
0.5-0.6	31
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	Natural Product ID
0.7679	Intermediate Similarity	NPC199204
0.5634	Remote Similarity	NPC307412
0.5634	Remote Similarity	NPC484110
0.5634	Remote Similarity	NPC606124
0.5606	Remote Similarity	NPC167111
0.5606	Remote Similarity	NPC318400
0.5493	Remote Similarity	NPC195343
0.5493	Remote Similarity	NPC267412
0.5493	Remote Similarity	NPC74655
0.5429	Remote Similarity	NPC166672
0.5417	Remote Similarity	NPC84894
0.5417	Remote Similarity	NPC18804
0.5417	Remote Similarity	NPC319859
0.5417	Remote Similarity	NPC164269
0.5417	Remote Similarity	NPC198381
0.5417	Remote Similarity	NPC287182
0.5417	Remote Similarity	NPC127888
0.5294	Remote Similarity	NPC26954
0.5294	Remote Similarity	NPC38099
0.5286	Remote Similarity	NPC476457
0.5278	Remote Similarity	NPC149320
0.5278	Remote Similarity	NPC160727
0.5278	Remote Similarity	NPC177281
0.5278	Remote Similarity	NPC471910
0.5238	Remote Similarity	NPC80170
0.5211	Remote Similarity	NPC86892
0.5211	Remote Similarity	NPC471909
0.5205	Remote Similarity	NPC128529
0.5205	Remote Similarity	NPC296624
0.5205	Remote Similarity	NPC55615
0.52	Remote Similarity	NPC471625
0.5132	Remote Similarity	NPC100986

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469675 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3420
0.1-0.2	5671
0.2-0.3	59
0.3-0.4	0
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