NPASS Compound

Natural Product: NPC141191

Natural Product ID	NPC141191
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Helenalin-[(2-Hydroxyethyl-3-Methyl)Acrylate]
IUPAC Name	[(3aR,5R,5aR,8aR,9S,9aR)-5,8a-dimethyl-1-methylidene-2,8-dioxo-3a,4,5,5a,9,9a-hexahydroazuleno[6,5-b]furan-9-yl] (Z)-2-(hydroxymethyl)but-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL517775
PubChem CID	11302856
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001543] Sesquiterpene lactones

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 50 52 0 0 0 0 0 0 0 0999 V2000 4.4939 -0.1228 1.7745 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5602 0.4873 0.4410 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4831 0.6752 -0.2973 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6712 1.3023 -1.6322 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9871 1.5975 -1.8943 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1637 0.2846 0.1755 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0242 -0.2444 1.3076 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0117 0.4677 -0.5745 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2794 0.0848 -0.1102 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1483 1.2927 0.1747 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1970 2.3317 0.6959 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5078 3.2123 0.0366 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2078 2.1661 2.1427 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4477 2.8597 2.9793 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0792 1.0962 2.4305 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0341 1.1298 1.3557 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0347 0.0796 1.3887 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7908 -1.1751 0.6341 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0104 -2.0648 0.7765 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4111 -0.8796 -0.7546 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8634 -1.7757 -1.8036 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9602 -1.7441 -2.7714 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8687 -0.8136 -2.3788 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1460 -0.1182 -3.1139 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9122 -0.9693 -0.9038 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4075 -2.3509 -0.5896 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5093 -0.2241 2.2216 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9005 0.4538 2.5096 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1285 -1.1868 1.6768 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5439 0.7952 0.0516 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2558 0.6568 -2.4383 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1137 2.2701 -1.5984 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5667 0.8122 -1.9977 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0996 -0.3550 0.9191 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5991 1.7392 -0.7152 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1682 3.9250 0.4792 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4222 3.2296 -1.0572 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5491 2.1275 1.4979 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2055 -0.2216 2.4674 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0450 0.4869 1.0830 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9573 -1.7257 1.1557 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7151 -1.9443 -0.0485 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4855 -1.8747 1.7699 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7093 -3.1423 0.8030 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7908 0.1276 -1.0142 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7791 -2.3800 -1.8196 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9914 -2.3045 -3.7242 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0615 -3.0991 -1.0683 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2068 -2.5265 0.4703 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5859 -2.4481 -1.1127 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 3 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 6 25 9 1 0 16 10 1 0 25 20 1 0 1 27 1 0 1 28 1 0 1 29 1 0 2 30 1 0 4 31 1 0 4 32 1 0 5 33 1 0 9 34 1 1 10 35 1 6 12 36 1 0 12 37 1 0 16 38 1 1 17 39 1 0 17 40 1 0 18 41 1 1 19 42 1 0 19 43 1 0 19 44 1 0 20 45 1 6 21 46 1 0 22 47 1 0 26 48 1 0 26 49 1 0 26 50 1 0 M END

Standard InCHIKey	KIURVBZLCHKNCM-FHUYBAJXSA-N
Standard InCHI	InChI=1S/C20H24O6/c1-5-12(9-21)19(24)26-17-16-11(3)18(23)25-14(16)8-10(2)13-6-7-15(22)20(13,17)4/h5-7,10,13-14,16-17,21H,3,8-9H2,1-2,4H3/b12-5-/t10-,13+,14-,16-,17+,20+/m1/s1
SMILES	C/C=C(/CO)C(=O)O[C@H]1[C@@H]2C(=C)C(=O)O[C@@H]2C[C@@H](C)[C@@H]2C=CC(=O)[C@@]12C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	360.16	Volume:	365.729 ? Van der Waals volume.
Dense:	0.985	LogP:	1.126 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.492 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.918 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	20.0
TPSA:	89.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.609	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.003	Fsp³:	0.55
MCE-18:	53.935 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.44	Fluc inhibitor:	0.09 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.022 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.013 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.402	Promiscuous compounds:	0.42

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.015	MDCK Permeability:	-4.645
Pgp-inhibitor:	0.349	Pgp-substrate:	0.017
PAMPA:	0.791 ? 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):	0.023
20% Bioavailability (F20%):	0.321	30% Bioavailability (F30%):	0.813
50% Bioavailability (F50%):	0.94

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.901
Plasma Protein Binding (PPB):	86.757%	Volume Distribution (VD):	0.066
Fu:	14.971% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.002
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.22	CYP3A4-substrate:	0.872
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.991
HLM stability:	0.069 ? 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):

6.788

Half-life (T1/2):

0.867

ADMET: Toxicity

hERG Blockers:	0.009	hERG Blockers (10um):	0.097
Human Hepatotoxicity (H-HT):	0.81	Drug-induced Liver Injury (DILI):	0.925
AMES Toxicity:	0.908	Rat Oral Acute Toxicity:	0.396
Maximum Recommended Daily Dose:	0.654	Skin Sensitization:	0.999
Carcinogencity:	0.957	Eye Corrosion:	0.323
Eye Irritation:	0.928	Respiratory Toxicity:	0.556
Drug-induced Neurotoxicity:	0.421	Ototoxicity:	0.405
Hematotoxicity:	0.841	Drug-induced Nephrotoxicity:	0.944
Genotoxicity:	0.966	RPMI-8226 Immunitoxicity:	0.19
A549 Cytotoxicity:	0.258	Hek293 Cytotoxicity:	0.307
BCF:	0.592 ? 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:	3.229 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.841 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.283 ? 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
NPO24121	Vernoniopsis caudata	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[15921436]
NPO24121	Vernoniopsis caudata	n.a.	n.a.	n.a.	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
IC50	2

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
NPT91	Cell line	KB	Homo sapiens	IC50	=	930.0	nM	PMID[21044847]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	190.0	nM	PMID[24972328]

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 NPC141191 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	15853
0.1-0.2	29559
0.2-0.3	3935
0.3-0.4	435
0.4-0.5	46
0.5-0.6	17
0.6-0.7	3
0.7-0.8	0
0.8-0.85	4
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8542	High Similarity	NPC607377
0.8235	Intermediate Similarity	NPC169205
0.8125	Intermediate Similarity	NPC123177
0.8125	Intermediate Similarity	NPC70595
0.8125	Intermediate Similarity	NPC150978
0.78	Intermediate Similarity	NPC74103
0.78	Intermediate Similarity	NPC604741
0.75	Intermediate Similarity	NPC610944
0.6111	Remote Similarity	NPC90121
0.6071	Remote Similarity	NPC284185
0.6071	Remote Similarity	NPC610110
0.5932	Remote Similarity	NPC185553
0.5893	Remote Similarity	NPC253144
0.5862	Remote Similarity	NPC171759
0.5849	Remote Similarity	NPC21471
0.5849	Remote Similarity	NPC33570
0.569	Remote Similarity	NPC203659
0.5536	Remote Similarity	NPC193645
0.5536	Remote Similarity	NPC48803
0.5536	Remote Similarity	NPC275960
0.5455	Remote Similarity	NPC161957
0.5439	Remote Similarity	NPC54843
0.5424	Remote Similarity	NPC604654
0.5263	Remote Similarity	NPC289004
0.5179	Remote Similarity	NPC70555
0.5179	Remote Similarity	NPC104961
0.5172	Remote Similarity	NPC70422
0.5167	Remote Similarity	NPC18019

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC141191 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5975
0.1-0.2	3138
0.2-0.3	35
0.3-0.4	1
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
0.5536	Remote Similarity	NPD1698	Clinical (unspecified phase)

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