NPASS Compound

Natural Product: NPC127824

Natural Product ID	NPC127824
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1E,3E,7R,8R,11E)-1-(2-Methoxypropan-2-Yl)-4,8,12-Trimethyloxabicyclo[12.1.0]-Pentadeca-1,3,11-Triene
IUPAC Name	(1R,4E,6E,10E,14S)-7-(2-methoxypropan-2-yl)-4,10,14-trimethyl-15-oxabicyclo[12.1.0]pentadeca-4,6,10-triene
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1761952
PubChem CID	54584323
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0000008] Cembrane diterpenoids

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 57 58 0 0 0 0 0 0 0 0999 V2000 -3.6196 -1.2618 1.4359 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6388 -1.4834 0.0946 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2579 -0.4802 -0.7344 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7334 -0.1429 -0.5899 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0809 -1.1263 -0.1041 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2434 -1.4924 0.3039 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6256 -2.6883 0.7399 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3000 -3.8452 0.8617 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0324 -2.9074 1.1798 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9434 -1.7271 1.1335 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4203 -1.1534 -0.1077 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6114 -0.4962 -1.1072 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4605 0.2631 -0.3396 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0397 1.2484 0.6715 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3095 2.4597 0.1594 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9543 2.0553 -0.3611 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1463 2.6652 -0.0078 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5236 2.2834 -0.5173 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4596 1.0817 -1.3965 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0885 3.8229 0.9622 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6360 0.8010 -1.2065 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4084 -0.8765 -2.1646 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0850 0.7666 -0.5159 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6225 -0.9792 1.7909 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4202 -0.5842 1.8012 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8395 -2.2355 1.9725 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7060 -2.0603 0.0369 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9387 -0.6895 0.3620 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9129 -3.9337 -0.0590 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2303 -4.7795 1.0271 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0184 -3.6961 1.7047 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0461 -3.3936 2.2013 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5096 -3.6834 0.5282 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8015 -1.9785 1.8488 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3843 -0.9328 1.7359 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2208 -1.7412 -0.6940 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5461 0.8671 1.5899 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0144 1.6824 1.1121 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8994 2.9708 -0.6232 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1666 3.1279 1.0556 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9238 1.2237 -1.0458 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1208 2.0936 0.4249 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0087 3.1573 -0.9946 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6048 1.0454 -2.0867 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3032 1.2326 -2.1875 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7427 4.5225 0.6525 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0358 3.4836 1.9947 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0069 4.4283 0.8275 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9650 0.0507 -1.9226 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2723 1.6862 -1.7666 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4125 1.1612 -0.5099 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1819 -0.2525 -2.6980 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6454 -1.9597 -2.2668 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4838 -0.7089 -2.7736 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2197 1.0470 0.5409 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1230 0.4580 -0.8434 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8269 1.6041 -1.1253 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 17 20 1 0 13 21 1 6 3 22 1 0 3 23 1 0 19 4 1 0 13 11 1 0 1 24 1 0 1 25 1 0 1 26 1 0 5 27 1 0 6 28 1 0 8 29 1 0 8 30 1 0 8 31 1 0 9 32 1 0 9 33 1 0 10 34 1 0 10 35 1 0 11 36 1 6 14 37 1 0 14 38 1 0 15 39 1 0 15 40 1 0 16 41 1 0 18 42 1 0 18 43 1 0 19 44 1 0 19 45 1 0 20 46 1 0 20 47 1 0 20 48 1 0 21 49 1 0 21 50 1 0 21 51 1 0 22 52 1 0 22 53 1 0 22 54 1 0 23 55 1 0 23 56 1 0 23 57 1 0 M END

Standard InCHIKey	IVESFYBFQSGMDH-YMYVTDHFSA-N
Standard InCHI	InChI=1S/C21H34O2/c1-16-8-7-15-21(5)19(23-21)14-11-17(2)10-13-18(12-9-16)20(3,4)22-6/h8,10,13,19H,7,9,11-12,14-15H2,1-6H3/b16-8+,17-10+,18-13+/t19-,21+/m1/s1
SMILES	COC(/C/1=C/C=C(C)/CC[C@H]2O[C@]2(CC/C=C(/CC1)C)C)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	318.26	Volume:	364.33 ? Van der Waals volume.
Dense:	0.874	LogP:	4.408 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.499 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.446 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	16.0
TPSA:	21.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.478	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.565	Fsp³:	0.714
MCE-18:	39.111 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.365	Fluc inhibitor:	0.017 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.056 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.964	Promiscuous compounds:	0.109

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.833	MDCK Permeability:	-4.788
Pgp-inhibitor:	0.997	Pgp-substrate:	0.025
PAMPA:	0.002 ? 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%):	0.017	30% Bioavailability (F30%):	0.029
50% Bioavailability (F50%):	0.46

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.913
Plasma Protein Binding (PPB):	96.221%	Volume Distribution (VD):	0.3
Fu:	4.01% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.968	BCRP inhibitor:	0.024
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.989	CYP1A2-substrate:	0.683
CYP2C19-inhibitor:	0.993	CYP2C19-substrate:	0.082
CYP2C9-inhibitor:	0.616	CYP2C9-substrate:	0.033
CYP2D6-inhibitor:	0.937	CYP2D6-substrate:	0.593
CYP3A4-inhibitor:	0.897	CYP3A4-substrate:	0.99
CYP2B6-substrate:	0.975	CYP2C8-inhibitor:	0.828
HLM stability:	0.851 ? 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):

11.385

Half-life (T1/2):

0.801

ADMET: Toxicity

hERG Blockers:	0.118	hERG Blockers (10um):	0.235
Human Hepatotoxicity (H-HT):	0.71	Drug-induced Liver Injury (DILI):	0.681
AMES Toxicity:	0.214	Rat Oral Acute Toxicity:	0.272
Maximum Recommended Daily Dose:	0.824	Skin Sensitization:	0.837
Carcinogencity:	0.287	Eye Corrosion:	0.011
Eye Irritation:	0.927	Respiratory Toxicity:	0.292
Drug-induced Neurotoxicity:	0.667	Ototoxicity:	0.199
Hematotoxicity:	0.115	Drug-induced Nephrotoxicity:	0.295
Genotoxicity:	0.446	RPMI-8226 Immunitoxicity:	0.15
A549 Cytotoxicity:	0.075	Hek293 Cytotoxicity:	0.469
BCF:	2.858 ? 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:	4.624 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.678 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.486 ? 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
NPO4638	Cynoglossum gansuense	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1860	Ceratium reticulatum	Species	Ceratiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO943	Carex nigra	Species	Cyperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6518	Aspilia laevissima	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5562	Armillaria novae-zelandiae	Species	Physalacriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2783	Lobophytum sarcophytoides	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29	Laburnum alpinum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26304	Hymenocallis littoralis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26304	Hymenocallis littoralis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26304	Hymenocallis littoralis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26304	Hymenocallis littoralis	Species	Amaryllidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO943	Carex nigra	Species	Cyperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1860	Ceratium reticulatum	Species	Ceratiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4638	Cynoglossum gansuense	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2783	Lobophytum sarcophytoides	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6518	Aspilia laevissima	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5562	Armillaria novae-zelandiae	Species	Physalacriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29	Laburnum alpinum	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

Activity Type	# Activity
EC50	1
IC50	1

Activity Type	# Activity
Individual protein	1
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3973	Individual protein	Endothelial PAS domain-containing protein 1	Homo sapiens	EC50	=	148900.0	nM	PMID[21353547]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	134200.0	nM	PMID[21353547]

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 NPC127824 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	29258
0.1-0.2	19787
0.2-0.3	680
0.3-0.4	90
0.4-0.5	30
0.5-0.6	10
0.6-0.7	3
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
0.6809	Remote Similarity	NPC607547
0.62	Remote Similarity	NPC475310
0.6038	Remote Similarity	NPC485434
0.5745	Remote Similarity	NPC604966
0.551	Remote Similarity	NPC56419
0.551	Remote Similarity	NPC606645
0.549	Remote Similarity	NPC485573
0.5385	Remote Similarity	NPC276290
0.5283	Remote Similarity	NPC143810
0.5283	Remote Similarity	NPC83838
0.5283	Remote Similarity	NPC605986
0.5283	Remote Similarity	NPC609177
0.5091	Remote Similarity	NPC489677

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC127824 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8193
0.1-0.2	938
0.2-0.3	17
0.3-0.4	1
0.4-0.5	1
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