NPASS Compound

Natural Product: NPC473766

Natural Product ID	NPC473766
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DWKWCVXACCMPGW-KCOSXCBVSA-N
IUPAC Name	n.a.
Synonyms	21-Acetylgedunin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL451271
PubChem CID	10506255
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 1.5006 4.0301 -1.6210 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4462 3.4113 -0.2872 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3154 4.0871 0.7467 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5432 2.0388 -0.1769 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5067 1.3242 1.0194 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8559 0.6095 1.0833 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9797 -0.2717 -0.1127 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8889 -1.2711 -0.3171 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5652 -0.6007 -0.1303 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3985 0.2654 1.0597 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6557 -0.4896 2.3684 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9544 0.8505 1.1433 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5953 0.7460 2.5048 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3031 2.0008 1.9768 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5077 2.7487 1.6231 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6523 3.9391 1.9240 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5256 2.0927 0.9222 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3332 0.6868 0.6079 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9302 0.5660 0.0395 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7983 -0.7484 -0.6259 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5984 -1.5625 -0.1349 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9227 1.6413 -1.0346 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4195 0.3124 -0.3082 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9188 1.0364 -1.3839 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9158 0.3107 -1.9587 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0341 -0.7872 -1.2929 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1629 -0.8510 -0.2840 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1060 -1.9980 0.6160 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2641 -1.9831 1.5384 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9965 -3.1665 0.4817 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0371 -2.5578 0.4373 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9608 -1.6431 -1.7648 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1559 -1.9383 -2.2402 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2935 -1.8817 -1.3417 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2022 -2.7328 -1.4229 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3735 -0.8094 -0.3275 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2639 0.2681 -0.9794 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0864 -1.2696 0.8838 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8839 3.3478 -2.3941 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4555 4.3044 -1.9370 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1566 4.9377 -1.6423 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3884 1.9901 1.8990 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0943 0.2093 2.0483 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6018 1.4480 0.9154 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8511 0.4514 -0.9876 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4375 0.0508 -1.0317 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2671 -1.0650 2.6744 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7217 0.3260 3.1484 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5614 -1.0512 2.4170 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4819 2.5108 2.5368 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4061 0.1431 1.5878 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6407 -1.4283 -0.6005 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5744 -0.6164 -1.7342 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4539 -2.3807 -0.8691 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7728 -1.9033 0.8854 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3755 1.1851 -1.9398 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9259 1.9753 -1.3436 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4924 2.5369 -0.7890 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5928 2.0297 -1.7368 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4865 0.6373 -2.8259 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5463 -3.9706 -0.1424 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2168 -3.5264 1.5175 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9221 -2.8245 -0.0123 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2301 -3.4509 -0.2342 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8715 -2.5910 1.1551 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0446 -2.8292 0.9068 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0830 -1.6700 -2.3890 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2805 -2.2236 -3.2992 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2931 -0.1299 -0.9807 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9583 0.3297 -2.0646 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1537 1.2329 -0.4823 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1509 -0.8915 0.9353 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2312 -2.3885 0.8028 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6157 -1.1086 1.8484 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 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 1 10 12 1 0 12 13 1 1 13 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 19 22 1 6 18 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 28 30 1 0 8 31 1 1 8 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 34 36 1 0 36 37 1 0 36 38 1 0 10 5 1 0 14 12 1 0 27 23 2 0 36 7 1 0 21 9 1 0 19 12 1 0 1 39 1 0 1 40 1 0 1 41 1 0 5 42 1 1 6 43 1 0 6 44 1 0 7 45 1 6 9 46 1 6 11 47 1 0 11 48 1 0 11 49 1 0 14 50 1 1 18 51 1 1 20 52 1 0 20 53 1 0 21 54 1 0 21 55 1 0 22 56 1 0 22 57 1 0 22 58 1 0 24 59 1 0 25 60 1 0 30 61 1 0 30 62 1 0 30 63 1 0 31 64 1 0 31 65 1 0 31 66 1 0 32 67 1 0 33 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	DWKWCVXACCMPGW-KCOSXCBVSA-N
Standard InCHI	InChI=1S/C30H36O8/c1-15(31)22-17(10-13-35-22)23-28(6)12-8-18-27(5)11-9-20(33)26(3,4)19(27)14-21(36-16(2)32)29(18,7)30(28)24(38-30)25(34)37-23/h9-11,13,18-19,21,23-24H,8,12,14H2,1-7H3/t18-,19+,21-,23+,24-,27-,28+,29+,30-/m1/s1
SMILES	CC(=O)O[C@@H]1C[C@@H]2[C@]([C@@H]3[C@]1(C)[C@@]14O[C@@H]1C(=O)O[C@H]([C@@]4(CC3)C)c1ccoc1C(=O)C)(C)C=CC(=O)C2(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	524.24	Volume:	527.964 ? Van der Waals volume.
Dense:	0.993	LogP:	2.152 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.428 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.264 ? 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:	5.691	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:	0.394	Fluc inhibitor:	0.023 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.02 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.193	Promiscuous compounds:	0.357

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.927	MDCK Permeability:	-4.741
Pgp-inhibitor:	0.994	Pgp-substrate:	0.033
PAMPA:	0.777 ? 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):	0.003
20% Bioavailability (F20%):	0.268	30% Bioavailability (F30%):	0.269
50% Bioavailability (F50%):	0.901

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.147	MRP1:	0.975
Plasma Protein Binding (PPB):	89.422%	Volume Distribution (VD):	0.099
Fu:	11.486% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.958	BCRP inhibitor:	0.128
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.028	CYP1A2-substrate:	0.075
CYP2C19-inhibitor:	0.395	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.03
CYP3A4-inhibitor:	0.966	CYP3A4-substrate:	0.383
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.97
HLM stability:	0.949 ? 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):

7.528

Half-life (T1/2):

0.573

ADMET: Toxicity

hERG Blockers:	0.076	hERG Blockers (10um):	0.395
Human Hepatotoxicity (H-HT):	0.719	Drug-induced Liver Injury (DILI):	0.878
AMES Toxicity:	0.666	Rat Oral Acute Toxicity:	0.895
Maximum Recommended Daily Dose:	0.981	Skin Sensitization:	0.918
Carcinogencity:	0.94	Eye Corrosion:	0.001
Eye Irritation:	0.655	Respiratory Toxicity:	0.857
Drug-induced Neurotoxicity:	0.226	Ototoxicity:	0.34
Hematotoxicity:	0.623	Drug-induced Nephrotoxicity:	0.753
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.322
A549 Cytotoxicity:	0.053	Hek293 Cytotoxicity:	0.356
BCF:	1.043 ? 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:	3.97 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.877 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.38 ? 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	=	31.0	%	PubChem BioAssay data set
NPT91	Cell line	KB	Homo sapiens	IC50	=	9.4	ug.mL-1	PMID[19110424]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.133	ug.mL-1	PMID[18183025]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.039	ug.mL-1	PMID[17562800]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Activity	=	29.38	%	PMID[22546674]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Activity	=	51.3	%	DrugMatrix in vitro pharmacology data

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 NPC473766 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	12829
0.1-0.2	34855
0.2-0.3	2069
0.3-0.4	58
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	NPC473753
0.7895	Intermediate Similarity	NPC209364
0.7895	Intermediate Similarity	NPC605015
0.6437	Remote Similarity	NPC302392
0.6235	Remote Similarity	NPC473473
0.6235	Remote Similarity	NPC475295
0.619	Remote Similarity	NPC286722
0.6047	Remote Similarity	NPC96443
0.6047	Remote Similarity	NPC290400
0.5904	Remote Similarity	NPC60973
0.5904	Remote Similarity	NPC605384
0.5882	Remote Similarity	NPC5079
0.5647	Remote Similarity	NPC107646
0.5647	Remote Similarity	NPC473368
0.5517	Remote Similarity	NPC197596
0.5506	Remote Similarity	NPC126723
0.5393	Remote Similarity	NPC475381
0.5349	Remote Similarity	NPC602263
0.5301	Remote Similarity	NPC474242
0.5227	Remote Similarity	NPC134254
0.5227	Remote Similarity	NPC335761
0.5169	Remote Similarity	NPC302369

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473766 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3721
0.1-0.2	5388
0.2-0.3	41
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