NPASS Compound

Natural Product: NPC307682

Natural Product ID	NPC307682
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methylgerambullone
IUPAC Name	(E)-N-[2-[4-[(2E)-3,7-dimethyl-5-oxoocta-2,6-dienoxy]phenyl]ethyl]-N-methyl-3-methylsulfonylprop-2-enamide
Synonyms	Methylgerambullone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL591333
PubChem CID	45258604
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001549] Monoterpenoids [CHEMONTID:0000051] Aromatic monoterpenoids

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 61 61 0 0 0 0 0 0 0 0999 V2000 -8.9840 -0.4747 -0.9555 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2559 -1.7272 -0.6625 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9901 -1.7480 -0.3337 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2237 -0.5321 -0.2375 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7804 0.5650 -0.4731 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7810 -0.6252 0.1430 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2420 0.7865 0.1640 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7329 1.3098 1.2649 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1749 2.6557 1.4296 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8544 2.7340 1.8294 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7005 2.2836 1.3143 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5912 1.5635 0.1535 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6291 1.1224 -0.3357 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7634 1.4244 0.3786 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7029 2.1464 1.5524 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4744 2.5665 2.0053 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1072 0.9629 -0.1205 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4446 -0.4116 0.4384 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7386 -0.7699 -0.0886 N 0 0 0 0 0 0 0 0 0 0 0 0 4.7834 -1.4968 -1.3630 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9476 -0.4540 0.5629 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9232 0.1634 1.6464 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2284 -0.8335 -0.0024 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3755 -0.5493 0.5886 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9307 -0.9941 -0.0697 S 0 0 0 0 0 0 0 0 0 0 0 0 10.3598 -2.2896 0.5423 O 0 0 0 0 0 0 0 0 0 0 0 0 10.9264 0.0910 0.2444 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8114 -1.2008 -1.8292 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3078 1.6127 -1.0616 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0007 -3.0184 -0.7466 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0426 -0.7087 -1.2550 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5395 0.0065 -1.8653 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0353 0.2276 -0.0948 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5049 -2.6916 -0.1293 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2065 -1.2530 -0.5542 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6952 -1.0252 1.1583 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7433 0.6337 2.1400 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8635 3.1912 2.1646 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2730 3.2955 0.5122 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4580 1.2928 -0.4465 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7077 0.5511 -1.2586 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6209 2.3828 2.1175 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4557 3.1326 2.9313 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8758 1.6977 0.1490 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0767 0.8623 -1.2216 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4387 -0.4126 1.5448 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7141 -1.1684 0.0968 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3685 -0.8666 -2.0666 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3525 -2.4435 -1.1712 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7820 -1.7488 -1.7114 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2836 -1.3786 -0.9563 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3071 -0.0104 1.5305 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9563 -1.8704 -2.0431 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7453 -1.7088 -2.1645 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6820 -0.1993 -2.2698 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2196 2.2529 -1.0845 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4401 2.2730 -1.1894 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4142 0.9335 -1.9394 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0822 -2.8897 -0.7184 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7289 -3.5242 -1.7115 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6472 -3.6965 0.0596 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 2 0 4 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 14 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 19 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 25 27 2 0 25 28 1 0 7 29 1 0 2 30 1 0 16 11 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 6 35 1 0 6 36 1 0 8 37 1 0 9 38 1 0 9 39 1 0 12 40 1 0 13 41 1 0 15 42 1 0 16 43 1 0 17 44 1 0 17 45 1 0 18 46 1 0 18 47 1 0 20 48 1 0 20 49 1 0 20 50 1 0 23 51 1 0 24 52 1 0 28 53 1 0 28 54 1 0 28 55 1 0 29 56 1 0 29 57 1 0 29 58 1 0 30 59 1 0 30 60 1 0 30 61 1 0 M END

Standard InCHIKey	XBMHYRIXEUNGGG-XKVHLQQPSA-N
Standard InCHI	InChI=1S/C23H31NO5S/c1-18(2)16-21(25)17-19(3)11-14-29-22-8-6-20(7-9-22)10-13-24(4)23(26)12-15-30(5,27)28/h6-9,11-12,15-16H,10,13-14,17H2,1-5H3/b15-12+,19-11+
SMILES	CC(=CC(=O)C/C(=C/COc1ccc(cc1)CCN(C)C(=O)/C=C/S(=O)(=O)C)/C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	433.19	Volume:	450.173 ? Van der Waals volume.
Dense:	0.962	LogP:	3.26 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.128 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.446 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	13.0
TPSA:	80.75 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	0.0	Rings:	1.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.394	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.03	Fsp³:	0.391
MCE-18:	13.0 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.361	Fluc inhibitor:	0.033 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.833 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.217	Promiscuous compounds:	0.027

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.872	MDCK Permeability:	-4.724
Pgp-inhibitor:	0.677	Pgp-substrate:	0.011
PAMPA:	0.132 ? 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):	0.349
20% Bioavailability (F20%):	0.125	30% Bioavailability (F30%):	0.295
50% Bioavailability (F50%):	0.469

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.451
Plasma Protein Binding (PPB):	92.04%	Volume Distribution (VD):	-0.017
Fu:	7.162% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.934	BCRP inhibitor:	0.01
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.991	CYP1A2-substrate:	0.95
CYP2C19-inhibitor:	0.115	CYP2C19-substrate:	0.111
CYP2C9-inhibitor:	0.843	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.383	CYP2D6-substrate:	0.016
CYP3A4-inhibitor:	0.241	CYP3A4-substrate:	0.011
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.979
HLM stability:	0.979 ? 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):

7.86

Half-life (T1/2):

0.7

ADMET: Toxicity

hERG Blockers:	0.565	hERG Blockers (10um):	0.214
Human Hepatotoxicity (H-HT):	0.971	Drug-induced Liver Injury (DILI):	0.985
AMES Toxicity:	0.437	Rat Oral Acute Toxicity:	0.076
Maximum Recommended Daily Dose:	0.957	Skin Sensitization:	0.987
Carcinogencity:	0.556	Eye Corrosion:	0.0
Eye Irritation:	0.006	Respiratory Toxicity:	0.972
Drug-induced Neurotoxicity:	0.598	Ototoxicity:	0.667
Hematotoxicity:	0.283	Drug-induced Nephrotoxicity:	0.608
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.369
A549 Cytotoxicity:	0.577	Hek293 Cytotoxicity:	0.881
BCF:	0.94 ? 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:	3.711 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.388 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.879 ? 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
NPO9943	Xanthostemon chrysanthus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27835	Salvia lutea	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3161	Populus cana	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13134	Iris japonica	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7071	Beilschmiedia brevipes	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12690	Caltha palustris	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12690	Caltha palustris	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13134	Iris japonica	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12690	Caltha palustris	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13134	Iris japonica	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12690	Caltha palustris	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9943	Xanthostemon chrysanthus	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3161	Populus cana	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13134	Iris japonica	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7071	Beilschmiedia brevipes	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12690	Caltha palustris	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27835	Salvia lutea	Species	Lamiaceae	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
Inhibition	3

Activity Type	# Activity
Tissue	3

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
NPT548	Tissue	Ileum	Cavia porcellus	Inhibition	=	45.31	%	PMID[19945876]
NPT548	Tissue	Ileum	Cavia porcellus	Inhibition	=	69.95	%	PMID[19945876]
NPT548	Tissue	Ileum	Cavia porcellus	Inhibition	=	78.66	%	PMID[19945876]

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 NPC307682 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	14229
0.1-0.2	34560
0.2-0.3	1014
0.3-0.4	45
0.4-0.5	9
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	Natural Product ID
0.7895	Intermediate Similarity	NPC309972

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC307682 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3309
0.1-0.2	5631
0.2-0.3	207
0.3-0.4	3
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