NPASS Compound

Natural Product: NPC470223

Natural Product ID	NPC470223
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-Oxo-24,25,26,27-Tetranortirucall-7-Ene-23(21)-Lactone
IUPAC Name	4-[(5R,9R,10R,13S,14S,17S)-4,4,10,13,14-pentamethyl-3-oxo-1,2,5,6,9,11,12,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]oxolan-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1835430
PubChem CID	12992564
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones

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 67 71 0 0 0 0 0 0 0 0999 V2000 -4.7675 -1.9638 -0.4626 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3482 -0.5135 -0.3610 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8782 -0.3553 -0.6465 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5699 0.7099 -1.6265 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1254 1.0238 -1.6634 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2354 0.5104 -0.8357 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6458 -0.4392 0.2093 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0700 -0.0711 0.6218 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5336 -0.8868 1.7891 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8984 -0.4213 2.2029 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7118 -0.0454 1.0137 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6860 0.6615 1.2201 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1107 1.3800 0.9824 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2568 -0.4690 1.3909 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6923 -0.5195 1.0270 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0832 -0.1782 -0.3749 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1904 0.8918 -0.9666 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6043 2.0616 -0.0910 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1275 1.8943 -0.0504 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4144 0.4492 -0.4134 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5728 -0.0889 0.2802 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6672 -0.2783 1.7235 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0806 -0.8486 1.7832 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9166 -0.6426 2.6928 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1952 -1.6234 0.6159 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0210 -1.4649 -0.1945 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5394 1.3266 -2.3511 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0207 -1.3817 -1.2967 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2122 0.2631 -1.3363 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0472 -2.2438 -1.4989 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7000 -2.0695 0.1438 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9820 -2.6647 -0.1470 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5054 -1.3249 -1.0386 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8656 0.3477 -2.6539 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0889 1.6719 -1.4151 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7840 1.7480 -2.4566 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7270 -1.4874 -0.1546 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8523 -0.6568 2.6342 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4661 -1.9679 1.6083 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4237 -1.1559 2.8491 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7813 0.4950 2.8176 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2117 1.8946 0.6359 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1515 1.4830 2.0953 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0237 1.9006 0.6108 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0624 -1.3755 1.9955 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0056 0.3763 2.0958 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2158 0.2050 1.6858 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0110 -1.5804 1.1774 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1636 2.0815 0.8929 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3949 3.0308 -0.5897 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5338 2.1727 0.9383 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6080 2.5806 -0.7910 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7236 0.4006 -1.5127 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4587 0.5697 -0.0126 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7060 0.6071 2.3489 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0965 -1.1302 2.1685 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2424 -1.4985 -1.2620 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3202 -2.2589 0.1509 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1571 0.6625 -3.1438 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0900 2.3720 -2.4468 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6012 1.5719 -2.5303 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0221 -2.3411 -0.7428 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8846 -1.3338 -2.0086 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1089 -1.3306 -1.9242 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8599 0.0364 -2.3589 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1427 1.3514 -1.1694 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2471 -0.1200 -1.2579 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 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 8 13 1 0 7 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 17 27 1 0 16 28 1 0 2 29 1 0 11 2 1 0 8 3 1 0 17 6 1 0 20 16 1 0 26 21 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 0 7 37 1 0 9 38 1 0 9 39 1 0 10 40 1 0 10 41 1 0 13 42 1 0 13 43 1 0 13 44 1 0 14 45 1 0 14 46 1 0 15 47 1 0 15 48 1 0 18 49 1 0 18 50 1 0 19 51 1 0 19 52 1 0 20 53 1 0 21 54 1 0 22 55 1 0 22 56 1 0 26 57 1 0 26 58 1 0 27 59 1 0 27 60 1 0 27 61 1 0 28 62 1 0 28 63 1 0 28 64 1 0 29 65 1 0 29 66 1 0 29 67 1 0 M END

Standard InCHIKey	BWKLKUMHNBYPDA-OGDHKUTASA-N
Standard InCHI	InChI=1S/C26H38O3/c1-23(2)20-7-6-19-18(24(20,3)11-10-21(23)27)9-13-25(4)17(8-12-26(19,25)5)16-14-22(28)29-15-16/h6,16-18,20H,7-15H2,1-5H3/t16?,17-,18-,20-,24+,25-,26+/m0/s1
SMILES	CC1(C2CC=C3C(C2(CCC1=O)C)CCC4(C3(CCC4C5CC(=O)OC5)C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	398.28	Volume:	433.931 ? Van der Waals volume.
Dense:	0.918	LogP:	3.492 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.534 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.719 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	27.0
TPSA:	43.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.419	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.636	Fsp³:	0.846
MCE-18:	92.083 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.197	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.544	Promiscuous compounds:	0.003

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.781	MDCK Permeability:	-4.788
Pgp-inhibitor:	0.776	Pgp-substrate:	0.0
PAMPA:	0.008 ? 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%):	0.0	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.271

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.731	MRP1:	0.999
Plasma Protein Binding (PPB):	94.788%	Volume Distribution (VD):	0.337
Fu:	5.169% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.142
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.005
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.623	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.015
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	0.977
HLM stability:	0.564 ? 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):

9.366

Half-life (T1/2):

0.405

ADMET: Toxicity

hERG Blockers:	0.072	hERG Blockers (10um):	0.423
Human Hepatotoxicity (H-HT):	0.739	Drug-induced Liver Injury (DILI):	0.506
AMES Toxicity:	0.163	Rat Oral Acute Toxicity:	0.203
Maximum Recommended Daily Dose:	0.854	Skin Sensitization:	0.891
Carcinogencity:	0.62	Eye Corrosion:	0.004
Eye Irritation:	0.227	Respiratory Toxicity:	0.35
Drug-induced Neurotoxicity:	0.827	Ototoxicity:	0.818
Hematotoxicity:	0.304	Drug-induced Nephrotoxicity:	0.421
Genotoxicity:	0.089	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.362	Hek293 Cytotoxicity:	0.465
BCF:	1.659 ? 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:	4.534 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.842 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.285 ? 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
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	twigs and leaves	Yunnan Province, China	2008-OCT	PMID[21954912]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[21954912]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	twig	n.a.	PMID[21954912]
NPO11885	Dysoxylum lenticellatum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11885	Dysoxylum lenticellatum	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
Activity	1

Activity Type	# Activity
Tissue	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
NPT177	Tissue	Aorta	Rattus norvegicus	Activity	=	43.5	%	PMID[20674349]

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 NPC470223 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	24211
0.1-0.2	21722
0.2-0.3	3499
0.3-0.4	323
0.4-0.5	53
0.5-0.6	27
0.6-0.7	19
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
0.7143	Intermediate Similarity	NPC470050
0.7143	Intermediate Similarity	NPC470051
0.6885	Remote Similarity	NPC470224
0.6818	Remote Similarity	NPC273669
0.6818	Remote Similarity	NPC484802
0.6818	Remote Similarity	NPC118647
0.6667	Remote Similarity	NPC470078
0.6508	Remote Similarity	NPC470052
0.6406	Remote Similarity	NPC470047
0.6406	Remote Similarity	NPC470046
0.6269	Remote Similarity	NPC479667
0.625	Remote Similarity	NPC90652
0.625	Remote Similarity	NPC155255
0.625	Remote Similarity	NPC470417
0.625	Remote Similarity	NPC260992
0.6212	Remote Similarity	NPC486521
0.6212	Remote Similarity	NPC262870
0.6119	Remote Similarity	NPC472239
0.6119	Remote Similarity	NPC67831
0.6119	Remote Similarity	NPC174051
0.6029	Remote Similarity	NPC605437
0.597	Remote Similarity	NPC471224
0.589	Remote Similarity	NPC189282
0.589	Remote Similarity	NPC237402
0.589	Remote Similarity	NPC484792
0.5797	Remote Similarity	NPC6190
0.5781	Remote Similarity	NPC247220
0.5714	Remote Similarity	NPC293081
0.5616	Remote Similarity	NPC63023
0.5616	Remote Similarity	NPC121566
0.5616	Remote Similarity	NPC100955
0.5616	Remote Similarity	NPC95243
0.5556	Remote Similarity	NPC73506
0.5429	Remote Similarity	NPC484798
0.5373	Remote Similarity	NPC82902
0.5373	Remote Similarity	NPC474218
0.5362	Remote Similarity	NPC147066
0.5352	Remote Similarity	NPC154101
0.5286	Remote Similarity	NPC28227
0.5278	Remote Similarity	NPC107243
0.5217	Remote Similarity	NPC171441
0.5217	Remote Similarity	NPC2983
0.5217	Remote Similarity	NPC472224
0.5217	Remote Similarity	NPC469994
0.5217	Remote Similarity	NPC472223
0.5205	Remote Similarity	NPC218383
0.5205	Remote Similarity	NPC474327
0.5067	Remote Similarity	NPC57416

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470223 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7177
0.1-0.2	1864
0.2-0.3	107
0.3-0.4	2
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