NPASS Compound

Natural Product: NPC473753

Natural Product ID	NPC473753
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ISWPEACHBAMEGH-LZFYJYPSSA-N
IUPAC Name	n.a.
Synonyms	23-Acetylgedunin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL450873
PubChem CID	10720857
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids [CHEMONTID:0002380] Limonoids

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 74 79 0 0 0 0 0 0 0 0999 V2000 7.9865 -2.0048 0.8762 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7449 -0.9613 -0.1810 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7164 -0.3108 -0.6023 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4187 -0.7114 -0.7030 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2254 -1.3489 -0.3411 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2149 -0.7898 -1.0942 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8410 0.1586 -1.8760 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1274 0.1759 -1.6201 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7574 -1.1485 -1.0560 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9521 -0.2425 -0.1598 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5884 -1.0036 1.0831 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1779 -1.4165 1.2413 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8159 -0.7166 0.3794 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2369 -0.8863 0.8495 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5623 -2.3158 0.6719 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5296 -2.8328 -0.0416 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4164 -1.9270 -0.7636 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0291 -2.2501 -1.8009 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5405 -0.5613 -0.1613 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1779 -0.0370 0.0853 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5289 0.3954 -1.2302 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4524 1.3886 -0.7852 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3927 0.6735 0.0655 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8577 0.5027 -0.8113 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7733 0.5752 -2.2227 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1287 1.6989 -1.5006 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8169 -0.1428 -3.0009 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1771 0.2660 -4.1531 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3323 -1.2525 -2.3706 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1446 1.5720 1.2217 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1711 2.3283 0.0030 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2163 3.6511 -0.3246 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6278 4.1044 -1.3351 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9922 4.5793 0.5520 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3837 -0.6510 1.0625 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2378 0.3859 -1.1303 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4133 -0.5922 2.3182 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9502 0.8419 0.3089 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9318 -1.7649 1.4049 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1248 -3.0098 0.4215 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1585 -1.9751 1.6131 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1600 -2.1343 0.4023 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3747 0.8095 -2.6022 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7436 -2.2083 -0.6491 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9947 -0.5220 2.0281 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1998 -1.9655 1.1108 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0858 -1.3197 2.3367 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0382 -2.5257 1.0562 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7815 -1.2691 -0.6137 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9135 -3.0289 1.2068 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7040 -3.9047 -0.1236 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3065 0.9248 0.6692 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1643 -0.4228 -1.8356 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2328 0.9892 -1.8510 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0128 1.9452 -1.6049 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1932 0.5450 -2.7947 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3641 2.4930 0.8119 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3379 1.1719 2.0964 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1404 1.9729 1.5772 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2131 4.0977 1.5279 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9265 4.9344 0.0462 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3405 5.4759 0.7587 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4199 -0.9480 0.7223 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5208 0.3367 1.5415 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0863 -1.4508 1.7704 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3503 0.3007 -1.0064 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9927 1.4377 -0.9236 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0269 0.0600 -2.1602 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6035 -0.0436 2.7874 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5816 -1.5101 2.9331 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3428 0.0269 2.4947 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8330 0.3405 0.7832 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2544 1.4850 -0.5348 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5064 1.4619 1.1102 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 6 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 2 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 25 27 1 0 27 28 2 0 27 29 1 0 23 30 1 0 22 31 1 0 31 32 1 0 32 33 2 0 32 34 1 0 19 35 1 0 19 36 1 0 14 37 1 0 10 38 1 0 8 4 1 0 29 9 1 0 24 10 1 0 23 13 1 0 20 14 1 0 26 24 1 0 1 39 1 0 1 40 1 0 1 41 1 0 5 42 1 0 7 43 1 0 9 44 1 0 11 45 1 0 11 46 1 0 12 47 1 0 12 48 1 0 13 49 1 0 15 50 1 0 16 51 1 0 20 52 1 0 21 53 1 0 21 54 1 0 22 55 1 0 25 56 1 0 30 57 1 0 30 58 1 0 30 59 1 0 34 60 1 0 34 61 1 0 34 62 1 0 35 63 1 0 35 64 1 0 35 65 1 0 36 66 1 0 36 67 1 0 36 68 1 0 37 69 1 0 37 70 1 0 37 71 1 0 38 72 1 0 38 73 1 0 38 74 1 0 M END

Standard InCHIKey	ISWPEACHBAMEGH-LZFYJYPSSA-N
Standard InCHI	InChI=1S/C30H36O8/c1-15(31)18-12-17(14-35-18)23-28(6)11-8-19-27(5)10-9-21(33)26(3,4)20(27)13-22(36-16(2)32)29(19,7)30(28)24(38-30)25(34)37-23/h9-10,12,14,19-20,22-24H,8,11,13H2,1-7H3/t19-,20+,22-,23+,24-,27-,28+,29+,30-/m1/s1
SMILES	CC(=O)C1=CC(=CO1)C2C3(CCC4C5(C=CC(=O)C(C5CC(C4(C36C(O6)C(=O)O2)C)OC(=O)C)(C)C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	524.24	Volume:	527.964 ? Van der Waals volume.
Dense:	0.993	LogP:	2.306 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.722 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.547 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	32.0
TPSA:	112.41 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.316	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.721	Fsp³:	0.667
MCE-18:	198.88 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.037	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.281 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.136	Promiscuous compounds:	0.017

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.978	MDCK Permeability:	-4.741
Pgp-inhibitor:	0.158	Pgp-substrate:	0.034
PAMPA:	0.188 ? 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%):	0.001	30% Bioavailability (F30%):	0.003
50% Bioavailability (F50%):	0.556

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.423	MRP1:	1.0
Plasma Protein Binding (PPB):	92.914%	Volume Distribution (VD):	0.071
Fu:	6.052% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.001
OATP1B3 inhibitor:	0.323	BCRP inhibitor:	0.001
BSEP inhibitor:	0.993

ADMET: Metabolism

CYP1A2-inhibitor:	0.076	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.051	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.041
CYP3A4-inhibitor:	0.938	CYP3A4-substrate:	0.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.891
HLM stability:	0.99 ? 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):

4.269

Half-life (T1/2):

0.691

ADMET: Toxicity

hERG Blockers:	0.053	hERG Blockers (10um):	0.352
Human Hepatotoxicity (H-HT):	0.434	Drug-induced Liver Injury (DILI):	0.758
AMES Toxicity:	0.361	Rat Oral Acute Toxicity:	0.416
Maximum Recommended Daily Dose:	0.883	Skin Sensitization:	0.292
Carcinogencity:	0.704	Eye Corrosion:	0.002
Eye Irritation:	0.262	Respiratory Toxicity:	0.358
Drug-induced Neurotoxicity:	0.315	Ototoxicity:	0.581
Hematotoxicity:	0.22	Drug-induced Nephrotoxicity:	0.14
Genotoxicity:	0.96	RPMI-8226 Immunitoxicity:	0.094
A549 Cytotoxicity:	0.163	Hek293 Cytotoxicity:	0.318
BCF:	0.841 ? 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:	3.913 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.967 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.178 ? 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
NPO20413	Meliaceae spp.	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9134742]
NPO20413	Meliaceae spp.	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20413	Meliaceae spp.	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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
Activity	3

Activity Type	# Activity
Cell line	2
Organism	4

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	Activity	=	38.0	%	PMID[26305406]
NPT91	Cell line	KB	Homo sapiens	IC50	=	10.9	ug.mL-1	PMID[8377014]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.832	ug.mL-1	PMID[1453184]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.156	ug.mL-1	PMID[21570834]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Activity	=	4.69	%	DOI[10.6019/CHEMBL1201861]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Activity	=	12.8	%	PMID[14510589]

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 NPC473753 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	12949
0.1-0.2	35129
0.2-0.3	1684
0.3-0.4	49
0.4-0.5	25
0.5-0.6	13
0.6-0.7	6
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
0.7949	Intermediate Similarity	NPC473766
0.7922	Intermediate Similarity	NPC209364
0.7922	Intermediate Similarity	NPC605015
0.6477	Remote Similarity	NPC302392
0.6235	Remote Similarity	NPC286722
0.6092	Remote Similarity	NPC96443
0.6092	Remote Similarity	NPC473473
0.6092	Remote Similarity	NPC290400
0.6092	Remote Similarity	NPC475295
0.5952	Remote Similarity	NPC60973
0.5952	Remote Similarity	NPC605384
0.593	Remote Similarity	NPC5079
0.5882	Remote Similarity	NPC107646
0.5556	Remote Similarity	NPC126723
0.5455	Remote Similarity	NPC335761
0.5444	Remote Similarity	NPC475381
0.5402	Remote Similarity	NPC602263
0.5341	Remote Similarity	NPC473368
0.5281	Remote Similarity	NPC134254
0.5222	Remote Similarity	NPC197596
0.5222	Remote Similarity	NPC302369
0.5176	Remote Similarity	NPC474242

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473753 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3719
0.1-0.2	5405
0.2-0.3	26
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