NPASS Compound

Natural Product: NPC474906

Natural Product ID	NPC474906
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ailanthinone
IUPAC Name	n.a.
Synonyms	NSC-238187
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL487194
PubChem CID	44559321
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0002119] Quassinoids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 68 72 0 0 0 0 0 0 0 0999 V2000 9.6362 -0.8605 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1371 -0.8081 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6380 -0.7558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5856 -2.2549 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1389 -0.7034 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1949 -1.8691 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4347 0.6210 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9356 0.6734 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5090 0.2098 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5316 -1.1703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8098 -2.6442 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1283 -1.7003 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 1.7537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2617 2.7574 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4086 3.6844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3694 0.1624 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2686 0.3011 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1328 3.1443 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2475 2.1406 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6741 2.6041 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9499 4.2246 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3764 3.7611 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6883 2.2939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1149 1.8303 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5736 1.2902 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8694 -0.0343 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6380 5.6918 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2458 -1.6317 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0090 -2.6782 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 11.1352 -0.9128 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5838 -2.3595 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6885 0.6386 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2678 -2.3024 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1894 0.6910 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6903 0.7433 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5333 -3.7539 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0672 -2.4895 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0913 -2.3856 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4976 -0.7174 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9226 -1.2320 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9913 -1.5156 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0881 -4.1182 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2838 -2.3659 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3808 -3.1001 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7310 -3.0739 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2143 -0.1736 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5862 3.4615 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8990 4.2129 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6713 2.2445 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5233 4.6881 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6521 4.7451 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7714 5.1399 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1946 4.0990 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6004 0.7041 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3907 -1.0037 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4912 4.7648 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7556 0.3667 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8134 -1.1999 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3261 7.1591 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1052 6.0037 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1389 5.7443 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6803 -1.1932 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7308 -4.1522 0.0000 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 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 6 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 6 21 22 1 0 19 23 1 0 23 24 1 0 24 25 2 0 17 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 1 0 26 32 1 0 13 33 1 1 12 34 1 0 24 8 1 0 20 9 1 0 22 13 1 0 20 14 1 0 30 15 1 0 1 35 1 0 1 36 1 0 1 37 1 0 2 38 1 0 2 39 1 0 3 40 1 0 4 41 1 0 4 42 1 0 4 43 1 0 8 44 1 1 9 45 1 6 10 46 1 6 11 47 1 0 11 48 1 0 11 49 1 0 12 50 1 6 14 51 1 1 16 52 1 0 16 53 1 0 16 54 1 0 17 55 1 1 18 56 1 0 18 57 1 0 19 58 1 6 21 59 1 0 21 60 1 0 27 61 1 0 30 62 1 1 31 63 1 0 32 64 1 0 32 65 1 0 32 66 1 0 33 67 1 0 34 68 1 0 M END

Standard InCHIKey	GCIFFNDSOLTCAI-ZTCIHUKBSA-N
Standard InCHI	InChI=1S/C25H34O9/c1-6-10(2)20(29)34-17-16-12(4)18(27)25(31)22-23(5)13(11(3)7-14(26)19(23)28)8-15(33-21(17)30)24(16,22)9-32-25/h7,10,12-13,15-19,22,27-28,31H,6,8-9H2,1-5H3/t10?,12-,13+,15-,16-,17-,18-,19-,22-,23-,24+,25-/m1/s1
SMILES	CCC(C)C(=O)O[C@@H]1[C@H]2[C@@H](C)[C@H]([C@@]3([C@@H]4[C@]5(C)[C@@H](C[C@H]([C@@]24CO3)OC1=O)C(=CC(=O)[C@H]5O)C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	478.22	Volume:	466.74 ? Van der Waals volume.
Dense:	1.025	LogP:	1.515 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.934 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.429 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	26.0
TPSA:	139.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	3.0	Rings:	5.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.501	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.565	Fsp³:	0.8
MCE-18:	132.378 ? 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:	0.467	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.015 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.111	Promiscuous compounds:	0.511

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.045	MDCK Permeability:	-4.689
Pgp-inhibitor:	0.001	Pgp-substrate:	0.996
PAMPA:	0.998 ? 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):	0.006
20% Bioavailability (F20%):	0.215	30% Bioavailability (F30%):	0.219
50% Bioavailability (F50%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.025	MRP1:	0.923
Plasma Protein Binding (PPB):	52.912%	Volume Distribution (VD):	-0.018
Fu:	53.751% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.857	BCRP inhibitor:	0.008
BSEP inhibitor:	0.874

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.016
CYP3A4-inhibitor:	0.98	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.374
HLM stability:	0.067 ? 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):

3.209

Half-life (T1/2):

2.518

ADMET: Toxicity

hERG Blockers:	0.018	hERG Blockers (10um):	0.324
Human Hepatotoxicity (H-HT):	0.584	Drug-induced Liver Injury (DILI):	0.359
AMES Toxicity:	0.703	Rat Oral Acute Toxicity:	0.678
Maximum Recommended Daily Dose:	0.821	Skin Sensitization:	0.999
Carcinogencity:	0.343	Eye Corrosion:	0.0
Eye Irritation:	0.163	Respiratory Toxicity:	0.9
Drug-induced Neurotoxicity:	0.383	Ototoxicity:	0.854
Hematotoxicity:	0.574	Drug-induced Nephrotoxicity:	0.952
Genotoxicity:	0.974	RPMI-8226 Immunitoxicity:	0.646
A549 Cytotoxicity:	0.045	Hek293 Cytotoxicity:	0.215
BCF:	0.633 ? 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:	3.446 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.26 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.391 ? 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
NPO32507	odyendyea gabonensis	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20738103]
NPO6324	Soulamea tomentosa	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7264678]
NPO6324	Soulamea tomentosa	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	3
T/C	1
GI50	2
Inhibition	1
ED50	4

Activity Type	# Activity
Cell line	5
Organism	1
Individual protein	1
Non-molecular	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT74	Individual protein	Proto-oncogene c-JUN	Homo sapiens	IC50	=	32.0	nM	PMID[18362187]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell line	P388	Mus musculus	T/C	=	148.0	%	PMID[7264678]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	3.4	nM	PubChem BioAssay data set
NPT90	Cell line	DU-145	Homo sapiens	ED50	=	0.09	uM	PMID[20516285]
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.13	uM	PMID[18524584]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.18	uM	PMID[20614907]
NPT992	Organism	Entamoeba histolytica	Entamoeba histolytica	IC50	=	0.063	ug.mL-1	PMID[17088494]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	31000.0	nM	PMID[19199792]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	<	25.0	%	PMID[19199792]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	0.37	uM	PMID[20738103]

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 NPC474906 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	18752
0.1-0.2	29215
0.2-0.3	1814
0.3-0.4	31
0.4-0.5	18
0.5-0.6	13
0.6-0.7	6
0.7-0.8	0
0.8-0.85	2
0.85-0.9	2
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC18547
0.8871	High Similarity	NPC485622
0.8871	High Similarity	NPC604056
0.8209	Intermediate Similarity	NPC485625
0.8088	Intermediate Similarity	NPC235539
0.7857	Intermediate Similarity	NPC297179
0.7746	Intermediate Similarity	NPC134869
0.7746	Intermediate Similarity	NPC152199
0.7681	Intermediate Similarity	NPC469877
0.6866	Remote Similarity	NPC201992
0.6571	Remote Similarity	NPC11252
0.6571	Remote Similarity	NPC289312
0.6184	Remote Similarity	NPC470628
0.6184	Remote Similarity	NPC608244
0.6026	Remote Similarity	NPC259306
0.5844	Remote Similarity	NPC96312
0.5844	Remote Similarity	NPC109607
0.5844	Remote Similarity	NPC328374
0.5833	Remote Similarity	NPC51978
0.5833	Remote Similarity	NPC604470
0.557	Remote Similarity	NPC470919
0.5432	Remote Similarity	NPC473798
0.5287	Remote Similarity	NPC470922
0.5263	Remote Similarity	NPC188667
0.5263	Remote Similarity	NPC204552
0.5263	Remote Similarity	NPC482434
0.5067	Remote Similarity	NPC143706
0.5065	Remote Similarity	NPC102822

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474906 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6566
0.1-0.2	2564
0.2-0.3	20
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