NPASS Compound

Natural Product: NPC471174

Natural Product ID	NPC471174
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	12Alpha-Acetoxy-7-Deacetylazadiron
IUPAC Name	[(5R,7R,8R,9R,10R,12S,13S,17S)-17-(furan-3-yl)-7-hydroxy-4,4,8,10,13-pentamethyl-3-oxo-5,6,7,9,11,12,16,17-octahydrocyclopenta[a]phenanthren-12-yl] acetate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2386305
PubChem CID	73356512
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 69 73 0 0 0 0 0 0 0 0999 V2000 4.4405 3.4735 1.0142 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3702 2.4759 1.2713 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0814 2.0558 2.3994 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5897 1.9186 0.2657 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5899 0.9968 0.4344 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1937 1.4679 0.1050 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7504 0.3331 -0.0918 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4758 -0.8954 0.7344 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8943 -1.3665 0.3624 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5274 -2.5210 0.3703 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9538 -2.3660 -0.1355 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1595 -0.9064 0.3395 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8818 -0.3422 -0.1877 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8867 -0.4019 -1.6705 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4059 -0.3162 -0.1022 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7899 0.5488 -1.0785 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1780 0.7165 -1.0040 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5846 -0.0210 -0.0229 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6170 -0.6462 0.5445 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4110 -0.5806 2.2387 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5553 -1.9081 0.5807 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1451 -3.2357 0.5877 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4287 -1.7420 -0.6268 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9029 -0.3652 -0.8844 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2024 0.7272 -0.1065 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8077 1.0697 1.1978 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3785 1.9493 -0.9242 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5430 2.1364 -1.5181 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6583 1.1877 -1.3983 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8489 1.5005 -1.6584 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3999 -0.2053 -0.9541 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1458 -0.6323 0.2512 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8467 -1.0914 -2.1290 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3782 3.9055 0.0165 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4140 2.9769 1.2048 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3389 4.2501 1.8238 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5750 0.7971 1.5324 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1943 2.0616 -0.8435 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2066 2.1445 0.8826 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5755 -0.0019 -1.1622 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1049 -3.4608 0.6942 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9606 -2.4805 -1.2078 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5936 -3.0579 0.4097 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1408 -1.0487 1.4741 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8613 -0.7415 -2.1038 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1919 -1.2502 -1.9781 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5347 0.4752 -2.2006 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1590 1.0502 -1.7938 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7940 1.3278 -1.6254 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7422 -1.3137 1.3838 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5654 0.4679 2.4715 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2093 -1.1385 2.8073 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5315 -1.0109 2.6905 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2845 -1.8687 1.4514 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1224 -3.5409 1.5267 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8972 -2.2402 -1.4762 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3401 -2.3899 -0.4646 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5907 -0.1642 -1.9655 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8869 0.3428 1.9742 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8038 1.5546 0.9661 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2189 1.9456 1.6026 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6180 2.6769 -1.0445 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7420 3.0102 -2.1334 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7631 0.2114 0.6769 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5283 -1.1248 1.0370 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9292 -1.4103 0.0046 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0763 -1.1032 -2.9292 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8253 -0.7212 -2.5000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9749 -2.1447 -1.8011 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 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 6 12 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 8 20 1 1 8 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 1 25 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 29 31 1 0 31 32 1 0 31 33 1 0 13 5 1 0 19 15 2 0 31 24 1 0 25 7 1 0 13 9 1 0 1 34 1 0 1 35 1 0 1 36 1 0 5 37 1 1 6 38 1 0 6 39 1 0 7 40 1 6 10 41 1 0 11 42 1 0 11 43 1 0 12 44 1 1 14 45 1 0 14 46 1 0 14 47 1 0 16 48 1 0 17 49 1 0 19 50 1 0 20 51 1 0 20 52 1 0 20 53 1 0 21 54 1 1 22 55 1 0 23 56 1 0 23 57 1 0 24 58 1 6 26 59 1 0 26 60 1 0 26 61 1 0 27 62 1 0 28 63 1 0 32 64 1 0 32 65 1 0 32 66 1 0 33 67 1 0 33 68 1 0 33 69 1 0 M END

Standard InCHIKey	XXVAKMOPFKOKNJ-FTEJKVAVSA-N
Standard InCHI	InChI=1S/C28H36O5/c1-16(29)33-24-14-21-26(4)11-9-22(30)25(2,3)20(26)13-23(31)28(21,6)19-8-7-18(27(19,24)5)17-10-12-32-15-17/h8-12,15,18,20-21,23-24,31H,7,13-14H2,1-6H3/t18-,20-,21+,23+,24-,26-,27-,28-/m0/s1
SMILES	CC(=O)O[C@H]1C[C@H]2[C@@](C3=CC[C@H]([C@]13C)c1ccoc1)(C)[C@H](O)C[C@@H]1[C@]2(C)C=CC(=O)C1(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	452.26	Volume:	478.194 ? Van der Waals volume.
Dense:	0.946	LogP:	2.593 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.751 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.891 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	27.0
TPSA:	76.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.492	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.13	Fsp³:	0.643
MCE-18:	126.783 ? 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:	0.732	Fluc inhibitor:	0.014 ? 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:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.123	Promiscuous compounds:	0.163

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.12	MDCK Permeability:	-4.734
Pgp-inhibitor:	0.892	Pgp-substrate:	0.074
PAMPA:	0.948 ? 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):	0.028
20% Bioavailability (F20%):	0.738	30% Bioavailability (F30%):	0.669
50% Bioavailability (F50%):	0.92

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.892
Plasma Protein Binding (PPB):	90.531%	Volume Distribution (VD):	-0.147
Fu:	9.345% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.842	BCRP inhibitor:	0.103
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.021
CYP2C19-inhibitor:	0.067	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.018
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.033
CYP3A4-inhibitor:	0.042	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.939
HLM stability:	0.424 ? 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):

11.207

Half-life (T1/2):

0.773

ADMET: Toxicity

hERG Blockers:	0.108	hERG Blockers (10um):	0.184
Human Hepatotoxicity (H-HT):	0.423	Drug-induced Liver Injury (DILI):	0.742
AMES Toxicity:	0.178	Rat Oral Acute Toxicity:	0.909
Maximum Recommended Daily Dose:	0.983	Skin Sensitization:	0.258
Carcinogencity:	0.865	Eye Corrosion:	0.0
Eye Irritation:	0.171	Respiratory Toxicity:	0.901
Drug-induced Neurotoxicity:	0.087	Ototoxicity:	0.642
Hematotoxicity:	0.215	Drug-induced Nephrotoxicity:	0.755
Genotoxicity:	0.972	RPMI-8226 Immunitoxicity:	0.111
A549 Cytotoxicity:	0.089	Hek293 Cytotoxicity:	0.214
BCF:	0.676 ? 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:	3.462 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.304 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.586 ? 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
NPO10033	Turraea pubescens	Species	Meliaceae	Eukaryota	twig	Dongfang, Hainan Province, China	2010-Mar	PMID[23734701]
NPO10033	Turraea pubescens	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10033	Turraea pubescens	Species	Meliaceae	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
mortality	3

Activity Type	# Activity
Cell line	2
Organism	3

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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	=	11900.0	nM	PMID[7561907]
NPT116	Cell line	HL-60	Homo sapiens	IC50	<	10000.0	nM	PMID[12828466]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT176	Organism	Artemia salina	Artemia salina	mortality	=	20.6	%	PMID[23734701]
NPT176	Organism	Artemia salina	Artemia salina	mortality	=	83.5	%	PMID[23734701]
NPT176	Organism	Artemia salina	Artemia salina	mortality	=	85.0	%	PMID[23734701]

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 NPC471174 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	8553
0.1-0.2	37487
0.2-0.3	3624
0.3-0.4	128
0.4-0.5	44
0.5-0.6	18
0.6-0.7	2
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
0.7105	Intermediate Similarity	NPC216755
0.6842	Remote Similarity	NPC56197
0.6506	Remote Similarity	NPC155939
0.5909	Remote Similarity	NPC141538
0.5854	Remote Similarity	NPC234494
0.5843	Remote Similarity	NPC296807
0.5769	Remote Similarity	NPC185456
0.5679	Remote Similarity	NPC238843
0.5679	Remote Similarity	NPC199044
0.5476	Remote Similarity	NPC272590
0.5422	Remote Similarity	NPC470790
0.5412	Remote Similarity	NPC197596
0.5301	Remote Similarity	NPC35000
0.5287	Remote Similarity	NPC34056
0.5238	Remote Similarity	NPC663
0.5238	Remote Similarity	NPC224394
0.5233	Remote Similarity	NPC156189
0.5233	Remote Similarity	NPC92979
0.5165	Remote Similarity	NPC470789
0.5116	Remote Similarity	NPC470997
0.5056	Remote Similarity	NPC470791

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471174 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3329
0.1-0.2	5747
0.2-0.3	74
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