NPASS Compound

Natural Product: NPC112680

Natural Product ID	NPC112680
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Isoiguesterin
IUPAC Name	(6aS,6bS,8aR,12aR,14aR)-3-hydroxy-4,6a,6b,8a,14a-pentamethyl-11-methylidene-7,8,9,10,12,12a,13,14-octahydropicen-2-one
Synonyms	Isoiguesterin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL454064
PubChem CID	328559
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0001831] Carbonyl compounds [CHEMONTID:0000118] Ketones [CHEMONTID:0003487] Cyclic ketones

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 66 70 0 0 0 0 0 0 0 0999 V2000 5.4232 1.8083 1.0744 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6533 0.7485 1.0332 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9247 -0.3606 2.0090 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7877 -1.3421 1.8288 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4828 -0.5459 2.0404 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8094 0.2295 3.3335 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4081 -1.5200 2.3226 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0633 -1.2887 1.7471 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1228 -0.0322 0.9416 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4048 1.1008 1.8694 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3129 -0.1487 0.0146 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1782 -1.0839 0.2883 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3763 -1.3464 -0.4983 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5966 -0.6018 -1.5429 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8283 -0.9152 -2.3117 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0663 -0.1954 -3.3912 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1461 0.8602 -3.7969 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3648 1.5638 -4.8413 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9582 1.1340 -3.0194 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6728 0.4341 -1.9169 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4910 0.7642 -1.1058 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8202 2.1989 -0.5819 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2251 0.9505 -1.9231 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9463 1.1907 -0.9888 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0689 0.1182 0.0505 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2048 -1.1848 -0.7223 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2622 0.4004 0.9086 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5248 0.5882 0.0696 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1973 -0.3980 -4.1985 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7526 -1.9585 -1.9258 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3065 2.6685 0.4064 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2308 1.8887 1.7862 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0516 -0.0113 3.0311 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8759 -0.8320 1.6655 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7759 -2.1250 2.6130 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8698 -1.7599 0.8330 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3645 1.1339 3.0858 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3496 -0.4612 4.0365 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8630 0.4845 3.8132 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7794 -2.5784 2.1202 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2732 -1.5654 3.4515 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1414 -2.1558 1.0565 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7247 -1.3230 2.5259 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3221 0.8027 2.9470 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4795 1.4508 1.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2176 1.9860 1.7631 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0776 -1.7648 1.1590 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0758 -2.1274 -0.2444 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2800 1.9062 -3.3225 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9516 2.6875 -0.1591 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0398 2.7698 -1.5354 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7526 2.2161 -0.0271 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3541 1.8838 -2.5047 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0491 0.1443 -2.6566 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8573 1.0871 -1.6479 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9721 2.2142 -0.6035 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2031 -1.5773 -1.0139 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7191 -1.9785 -0.1909 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7497 -1.0324 -1.6856 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0998 1.4163 1.3573 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7040 -0.2578 -0.6055 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4308 1.5665 -0.4526 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2970 -1.2591 -4.7195 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3374 -2.9214 -1.6328 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3526 -1.5883 -1.0438 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5035 -2.1557 -2.7180 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 1 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 1 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 2 0 20 21 1 0 21 22 1 1 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 6 25 27 1 0 27 28 1 0 16 29 1 0 15 30 1 0 28 2 1 0 27 5 1 0 25 9 1 0 21 11 1 0 20 14 1 0 1 31 1 0 1 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 6 37 1 0 6 38 1 0 6 39 1 0 7 40 1 0 7 41 1 0 8 42 1 0 8 43 1 0 10 44 1 0 10 45 1 0 10 46 1 0 12 47 1 0 13 48 1 0 19 49 1 0 22 50 1 0 22 51 1 0 22 52 1 0 23 53 1 0 23 54 1 0 24 55 1 0 24 56 1 0 26 57 1 0 26 58 1 0 26 59 1 0 27 60 1 1 28 61 1 0 28 62 1 0 29 63 1 0 30 64 1 0 30 65 1 0 30 66 1 0 M END

Standard InCHIKey	RUVGAOXZLPFVKY-IPTPSVHJSA-N
Standard InCHI	InChI=1S/C28H36O2/c1-17-9-10-25(3)11-13-27(5)22-8-7-19-18(2)24(30)21(29)16-20(19)26(22,4)12-14-28(27,6)23(25)15-17/h7-8,16,23,30H,1,9-15H2,2-6H3/t23-,25-,26+,27-,28+/m1/s1
SMILES	C=C1CC[C@]2(C)CC[C@]3(C)C4=CC=C5C(=C(C(=O)C=C5[C@]4(C)CC[C@@]3(C)[C@@H]2C1)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	404.27	Volume:	451.823 ? Van der Waals volume.
Dense:	0.895	LogP:	3.428 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.24 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.961 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	28.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.435	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.919	Fsp³:	0.607
MCE-18:	88.667 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.907	Fluc inhibitor:	0.343 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.574 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.037 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.636	Promiscuous compounds:	0.384

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.049	MDCK Permeability:	-4.869
Pgp-inhibitor:	0.973	Pgp-substrate:	0.035
PAMPA:	0.35 ? 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%):	0.959	30% Bioavailability (F30%):	0.949
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.999	MRP1:	0.994
Plasma Protein Binding (PPB):	94.353%	Volume Distribution (VD):	0.419
Fu:	5.607% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.918
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.969	CYP1A2-substrate:	0.992
CYP2C19-inhibitor:	0.99	CYP2C19-substrate:	0.902
CYP2C9-inhibitor:	0.243	CYP2C9-substrate:	0.016
CYP2D6-inhibitor:	0.065	CYP2D6-substrate:	0.828
CYP3A4-inhibitor:	0.705	CYP3A4-substrate:	0.998
CYP2B6-substrate:	0.004	CYP2C8-inhibitor:	0.996
HLM stability:	0.995 ? 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):

4.864

Half-life (T1/2):

0.548

ADMET: Toxicity

hERG Blockers:	0.264	hERG Blockers (10um):	0.329
Human Hepatotoxicity (H-HT):	0.831	Drug-induced Liver Injury (DILI):	0.945
AMES Toxicity:	0.49	Rat Oral Acute Toxicity:	0.81
Maximum Recommended Daily Dose:	0.874	Skin Sensitization:	0.932
Carcinogencity:	0.561	Eye Corrosion:	0.0
Eye Irritation:	0.299	Respiratory Toxicity:	0.971
Drug-induced Neurotoxicity:	0.915	Ototoxicity:	0.771
Hematotoxicity:	0.841	Drug-induced Nephrotoxicity:	0.871
Genotoxicity:	0.972	RPMI-8226 Immunitoxicity:	0.33
A549 Cytotoxicity:	0.512	Hek293 Cytotoxicity:	0.48
BCF:	2.346 ? 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:	4.759 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.054 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.707 ? 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
NPO26927	Salacia madagascariensis	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[15730255]
NPO26927	Salacia madagascariensis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15730255]
NPO26927	Salacia madagascariensis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7288445]
NPO26927	Salacia madagascariensis	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26927	Salacia madagascariensis	Species	Celastraceae	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
T/C	2
ED50	1
IC50	8
IC90	1

Activity Type	# Activity
Cell line	4
Organism	8

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
NPT168	Cell line	P388	Mus musculus	T/C	=	147.0	%	PMID[7288445]
NPT168	Cell line	P388	Mus musculus	T/C	=	125.0	%	PMID[7288445]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.24	ug ml-1	PubChem BioAssay data set
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	1.6	ug.mL-1	PMID[18443128]
NPT86	Organism	Mycobacterium intracellulare	Mycobacterium intracellulare	IC50	=	4.5	ug.mL-1	PMID[16933872]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.2	ug.mL-1	PMID[26225905]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.17	ug.mL-1	PubChem BioAssay data set
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	0.032	ug.mL-1	PMID[21737288]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC90	=	0.055	ug.mL-1	PMID[19114678]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	0.85	ug.mL-1	PMID[22071302]
NPT842	Organism	Leishmania mexicana	Leishmania mexicana	IC50	=	0.035	ug.mL-1	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 NPC112680 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	24767
0.1-0.2	23819
0.2-0.3	1251
0.3-0.4	6
0.4-0.5	2
0.5-0.6	0
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8103	Intermediate Similarity	NPC53385
0.7966	Intermediate Similarity	NPC33881
0.7581	Intermediate Similarity	NPC263780
0.7333	Intermediate Similarity	NPC292589
0.6935	Remote Similarity	NPC309309
0.6935	Remote Similarity	NPC291999
0.6774	Remote Similarity	NPC65615
0.6774	Remote Similarity	NPC68148
0.6774	Remote Similarity	NPC287063
0.6719	Remote Similarity	NPC174167
0.6418	Remote Similarity	NPC112454
0.6176	Remote Similarity	NPC777
0.6154	Remote Similarity	NPC211230

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC112680 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7461
0.1-0.2	1642
0.2-0.3	46
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	1
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
0.6418	Remote Similarity	NPD7285	Clinical (unspecified phase)

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