NPASS Compound

Natural Product: NPC269509

Natural Product ID	NPC269509
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FOCCASNSHDSZLN-CGZYOCHMSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11953932
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 [CHEMONTID:0001771] Germacranolides 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 57 58 0 0 0 0 0 0 0 0999 V2000 -0.6345 1.2469 -2.5719 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8402 1.5551 -1.1293 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9804 1.7808 -0.5788 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3488 1.7855 -1.1867 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8402 0.3597 -0.6652 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0362 -0.6522 -1.3110 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9853 -1.2016 -0.8312 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3858 -0.9323 0.4265 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1214 -0.9269 0.3369 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4594 -1.1562 1.7699 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3357 -0.5907 2.5049 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4992 -2.2019 2.1499 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4529 -2.9517 3.1801 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4828 -2.2259 1.1654 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8716 0.0797 -0.3738 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4401 1.5273 -0.2944 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2534 0.0430 0.0034 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2709 -0.3178 -0.8659 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9172 -0.6208 -2.0361 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6706 -0.3527 -0.4760 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0624 -0.0405 0.7394 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5080 -0.0984 1.0671 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9732 1.1550 1.4724 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6821 -0.7510 -1.4763 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4116 -1.0102 -2.7344 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9715 0.3576 0.7046 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1606 0.3146 1.4033 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2323 0.2733 0.7459 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2532 0.3141 2.8845 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5185 0.1904 -2.8158 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3444 1.7309 -2.8636 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4063 1.7510 -3.2018 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9855 2.0116 0.5074 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9331 2.5695 -0.7067 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4051 1.8410 -2.2492 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8560 0.3209 -1.1037 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4829 -1.9750 -1.4622 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8051 -0.2697 1.1613 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3657 -1.9404 -0.1441 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4341 -0.9061 3.5580 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0085 0.1850 2.2212 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8780 -0.2420 -1.4774 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2824 1.8812 0.7137 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1520 2.1950 -0.8115 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3539 0.2553 1.4980 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6335 -0.8131 1.9107 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0866 -0.5090 0.2195 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5240 1.8720 0.9635 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1892 -0.9763 -2.4357 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4461 0.0340 -1.6443 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1660 -1.7093 -1.1508 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9313 -0.3087 -3.4175 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5186 -0.9919 -2.8456 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0756 -2.0275 -2.9831 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0983 -0.3510 3.1665 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5847 1.3484 3.1941 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3141 0.0720 3.3870 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 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 12 14 1 0 9 15 1 0 15 16 1 0 15 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 20 24 1 0 6 25 1 0 5 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 16 2 1 0 14 8 1 0 1 30 1 0 1 31 1 0 1 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 5 36 1 6 7 37 1 0 8 38 1 1 9 39 1 6 11 40 1 0 11 41 1 0 15 42 1 6 16 43 1 0 16 44 1 0 21 45 1 0 22 46 1 0 22 47 1 0 23 48 1 0 24 49 1 0 24 50 1 0 24 51 1 0 25 52 1 0 25 53 1 0 25 54 1 0 29 55 1 0 29 56 1 0 29 57 1 0 M END

Standard InCHIKey	FOCCASNSHDSZLN-CGZYOCHMSA-N
Standard InCHI	InChI=1S/C22H28O7/c1-12-6-7-17(27-16(5)24)14(3)11-19-20(15(4)22(26)29-19)18(10-12)28-21(25)13(2)8-9-23/h6,8,11,17-20,23H,4,7,9-10H2,1-3,5H3/b12-6+,13-8+,14-11-/t17-,18+,19+,20+/m0/s1
SMILES	C/C/1=CC[C@@H](/C(=C[C@@H]2[C@H](C(=C)C(=O)O2)[C@@H](C1)OC(=O)/C(=C/CO)/C)/C)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	404.18	Volume:	415.032 ? Van der Waals volume.
Dense:	0.974	LogP:	1.44 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.764 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.744 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	19.0
TPSA:	99.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.333	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.942	Fsp³:	0.5
MCE-18:	40.182 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.416	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.052 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.018 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.609	Promiscuous compounds:	0.374

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.765	MDCK Permeability:	-4.685
Pgp-inhibitor:	0.977	Pgp-substrate:	0.706
PAMPA:	0.528 ? 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):	0.598
20% Bioavailability (F20%):	0.975	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.915
Plasma Protein Binding (PPB):	60.837%	Volume Distribution (VD):	-0.311
Fu:	34.638% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.014
BSEP inhibitor:	0.93

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.054	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.164
CYP3A4-inhibitor:	0.079	CYP3A4-substrate:	0.27
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.927
HLM stability:	0.836 ? 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):

8.506

Half-life (T1/2):

0.901

ADMET: Toxicity

hERG Blockers:	0.003	hERG Blockers (10um):	0.04
Human Hepatotoxicity (H-HT):	0.887	Drug-induced Liver Injury (DILI):	0.982
AMES Toxicity:	0.72	Rat Oral Acute Toxicity:	0.108
Maximum Recommended Daily Dose:	0.477	Skin Sensitization:	1.0
Carcinogencity:	0.749	Eye Corrosion:	0.045
Eye Irritation:	0.711	Respiratory Toxicity:	0.133
Drug-induced Neurotoxicity:	0.266	Ototoxicity:	0.517
Hematotoxicity:	0.789	Drug-induced Nephrotoxicity:	0.923
Genotoxicity:	0.875	RPMI-8226 Immunitoxicity:	0.124
A549 Cytotoxicity:	0.412	Hek293 Cytotoxicity:	0.218
BCF:	0.621 ? 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:	3.437 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.413 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.674 ? 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
NPO2440	Schkuhria pinnata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29244495]
NPO691	Tarchonanthus camphoratus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29244495]
NPO2440	Schkuhria pinnata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO691	Tarchonanthus camphoratus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2440	Schkuhria pinnata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO691	Tarchonanthus camphoratus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2440	Schkuhria pinnata	Species	Asteraceae	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
IC50	2
Ratio IC50	1

Activity Type	# Activity
Cell line	1
Organism	1
Others	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
NPT839	Cell line	L6	Rattus norvegicus	IC50	=	7940.0	nM	PMID[29244495]
NPT844	Organism	Trypanosoma brucei rhodesiense	Trypanosoma brucei rhodesiense	IC50	=	1700.0	nM	PMID[29244495]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	4.6	n.a.	PMID[29244495]

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 NPC269509 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	18415
0.1-0.2	27765
0.2-0.3	3176
0.3-0.4	368
0.4-0.5	88
0.5-0.6	30
0.6-0.7	2
0.7-0.8	0
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8491	Intermediate Similarity	NPC134725
0.8491	Intermediate Similarity	NPC48657
0.8269	Intermediate Similarity	NPC482128
0.8269	Intermediate Similarity	NPC482129
0.8163	Intermediate Similarity	NPC476028
0.7719	Intermediate Similarity	NPC482132
0.7407	Intermediate Similarity	NPC482131
0.7167	Intermediate Similarity	NPC486033
0.7119	Intermediate Similarity	NPC486037
0.7119	Intermediate Similarity	NPC486034
0.7091	Intermediate Similarity	NPC266957
0.6964	Remote Similarity	NPC482130
0.6207	Remote Similarity	NPC482126
0.5909	Remote Similarity	NPC59330
0.5902	Remote Similarity	NPC482133
0.5862	Remote Similarity	NPC473321
0.5833	Remote Similarity	NPC470755
0.5833	Remote Similarity	NPC298801
0.5758	Remote Similarity	NPC486035
0.5738	Remote Similarity	NPC482127
0.569	Remote Similarity	NPC250940
0.569	Remote Similarity	NPC169575
0.5645	Remote Similarity	NPC488120
0.5645	Remote Similarity	NPC486031
0.5556	Remote Similarity	NPC488118
0.5538	Remote Similarity	NPC96018
0.5536	Remote Similarity	NPC603669
0.5536	Remote Similarity	NPC611318
0.55	Remote Similarity	NPC158756
0.55	Remote Similarity	NPC601035
0.5484	Remote Similarity	NPC471141
0.5357	Remote Similarity	NPC171204
0.5357	Remote Similarity	NPC606745
0.5345	Remote Similarity	NPC270126
0.5333	Remote Similarity	NPC488296
0.5312	Remote Similarity	NPC230800
0.5238	Remote Similarity	NPC469910
0.5205	Remote Similarity	NPC486036
0.5179	Remote Similarity	NPC97516
0.5156	Remote Similarity	NPC40746
0.5156	Remote Similarity	NPC488304
0.5156	Remote Similarity	NPC482134
0.5077	Remote Similarity	NPC475748

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC269509 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6736
0.1-0.2	2381
0.2-0.3	33
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