NPASS Compound

Natural Product: NPC188632

Natural Product ID	NPC188632
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Mammea A/Bb
IUPAC Name	5,7-dihydroxy-8-[(2S)-2-methylbutanoyl]-6-(3-methylbut-2-enyl)-4-phenylchromen-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1689186
PubChem CID	53322741
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0001614] Neoflavonoids [CHEMONTID:0003650] Prenylated neoflavonoids

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 56 58 0 0 0 0 0 0 0 0999 V2000 5.7581 -2.5807 -0.0089 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5090 -1.3433 -0.7927 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3606 -0.4852 -0.2250 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1421 -1.2778 -0.2386 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2604 -2.5441 -0.3975 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7686 -0.8008 -0.0919 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7113 -1.6918 -0.0867 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9626 -3.0705 -0.1966 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5969 -1.3156 0.0207 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6726 -2.3320 -0.0078 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0092 -1.8616 0.3227 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9739 -1.8988 -0.5710 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7017 -2.4241 -1.9281 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3230 -1.4163 -0.2135 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8506 0.0373 0.1289 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1417 1.0024 0.1296 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4604 0.5322 0.0166 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4326 1.3971 0.0154 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2126 2.6782 0.1154 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2033 3.4639 0.1087 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9686 3.2131 0.2267 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1228 2.3367 0.2331 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4673 2.8630 0.2647 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3857 2.8197 -0.7595 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6543 3.3582 -0.6521 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0521 3.9732 0.5152 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1627 4.0335 1.5531 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8973 3.4936 1.4398 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1674 0.4528 0.2494 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8335 -0.1508 1.1817 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3825 -3.4733 -0.5743 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8787 -2.7243 0.0566 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4214 -2.5762 1.0341 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2386 -1.6238 -1.8321 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4340 -0.7504 -0.8659 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3685 0.4402 -0.8061 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9691 -3.5835 0.6729 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4054 -3.2103 0.6631 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6803 -2.7735 -1.0524 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2264 -1.4911 1.3108 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3968 -3.4977 -1.9114 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6054 -2.3042 -2.5647 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8697 -1.8810 -2.4352 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5727 -0.4147 -0.5925 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1337 -2.1113 -0.5787 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4495 -1.4417 0.9054 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7342 4.2567 0.3112 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0762 2.3401 -1.6930 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3690 3.3145 -1.4764 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0628 4.3904 0.5686 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5079 4.5272 2.4610 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2097 3.5553 2.2785 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5441 0.7246 1.1756 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9518 0.0017 1.0978 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4656 0.7975 1.5828 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5778 -0.9526 1.9122 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 2 0 4 6 1 0 6 7 2 0 7 8 1 0 7 9 1 0 9 10 1 0 10 11 1 0 11 12 2 3 12 13 1 0 12 14 1 0 9 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 15 29 1 0 3 30 1 0 17 6 1 0 28 23 1 0 22 16 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 0 2 35 1 0 3 36 1 6 8 37 1 0 10 38 1 0 10 39 1 0 11 40 1 0 13 41 1 0 13 42 1 0 13 43 1 0 14 44 1 0 14 45 1 0 14 46 1 0 21 47 1 0 24 48 1 0 25 49 1 0 26 50 1 0 27 51 1 0 28 52 1 0 29 53 1 0 30 54 1 0 30 55 1 0 30 56 1 0 M END

Standard InCHIKey	ZZRRSYITGMMRPP-HNNXBMFYSA-N
Standard InCHI	InChI=1S/C25H26O5/c1-5-15(4)22(27)21-24(29)17(12-11-14(2)3)23(28)20-18(13-19(26)30-25(20)21)16-9-7-6-8-10-16/h6-11,13,15,28-29H,5,12H2,1-4H3/t15-/m0/s1
SMILES	CC[C@@H](C(=O)c1c(O)c(CC=C(C)C)c(c2c1oc(=O)cc2c1ccccc1)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	406.18	Volume:	432.873 ? Van der Waals volume.
Dense:	0.938	LogP:	5.389 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.935 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.023 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	20.0
TPSA:	87.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

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:	3.252	Fsp³:	0.28
MCE-18:	42.0 ? 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:	0.807	Fluc inhibitor:	0.066 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.856 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.839 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.214	Promiscuous compounds:	0.133

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.891	MDCK Permeability:	-4.641
Pgp-inhibitor:	0.937	Pgp-substrate:	0.117
PAMPA:	0.425 ? 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):	0.012
20% Bioavailability (F20%):	0.634	30% Bioavailability (F30%):	0.886
50% Bioavailability (F50%):	0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.035	MRP1:	0.989
Plasma Protein Binding (PPB):	97.905%	Volume Distribution (VD):	0.079
Fu:	1.707% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.945
OATP1B3 inhibitor:	0.686	BCRP inhibitor:	0.304
BSEP inhibitor:	0.981

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.985	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.801
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.042	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

2.853

Half-life (T1/2):

0.933

ADMET: Toxicity

hERG Blockers:	0.074	hERG Blockers (10um):	0.299
Human Hepatotoxicity (H-HT):	0.622	Drug-induced Liver Injury (DILI):	0.905
AMES Toxicity:	0.562	Rat Oral Acute Toxicity:	0.741
Maximum Recommended Daily Dose:	0.882	Skin Sensitization:	0.808
Carcinogencity:	0.457	Eye Corrosion:	0.0
Eye Irritation:	0.549	Respiratory Toxicity:	0.916
Drug-induced Neurotoxicity:	0.56	Ototoxicity:	0.349
Hematotoxicity:	0.433	Drug-induced Nephrotoxicity:	0.813
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.121
A549 Cytotoxicity:	0.296	Hek293 Cytotoxicity:	0.64
BCF:	1.689 ? 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:	4.903 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.465 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.075 ? 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
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21214226]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	stem	n.a.	PMID[21214226]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21645	Mammea americana	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21645	Mammea americana	Species	Calophyllaceae	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	4

Activity Type	# Activity
Cell line	2
Protein family	2

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
NPT396	Cell line	T47D	Homo sapiens	IC50	=	4010.0	nM	PMID[21214226]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	5260.0	nM	PMID[21214226]
NPT21802	Protein family	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	IC50	=	6760.0	nM	PMID[21214226]
NPT21802	Protein family	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	IC50	=	5960.0	nM	PMID[21214226]

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 NPC188632 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	10724
0.1-0.2	36808
0.2-0.3	2149
0.3-0.4	108
0.4-0.5	30
0.5-0.6	22
0.6-0.7	6
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC112791
0.9	High Similarity	NPC87609
0.8507	High Similarity	NPC469935
0.8281	Intermediate Similarity	NPC196137
0.791	Intermediate Similarity	NPC483434
0.7826	Intermediate Similarity	NPC178627
0.7313	Intermediate Similarity	NPC470296
0.7313	Intermediate Similarity	NPC196459
0.7123	Intermediate Similarity	NPC181388
0.6479	Remote Similarity	NPC1886
0.6338	Remote Similarity	NPC36181
0.6338	Remote Similarity	NPC94794
0.6081	Remote Similarity	NPC36705
0.6	Remote Similarity	NPC131782
0.6	Remote Similarity	NPC474624
0.5921	Remote Similarity	NPC19238
0.5833	Remote Similarity	NPC470909
0.5753	Remote Similarity	NPC219584
0.5658	Remote Similarity	NPC474738
0.5652	Remote Similarity	NPC32463
0.56	Remote Similarity	NPC73776
0.56	Remote Similarity	NPC329215
0.5584	Remote Similarity	NPC470322
0.5584	Remote Similarity	NPC475797
0.5571	Remote Similarity	NPC154217
0.5541	Remote Similarity	NPC262011
0.5526	Remote Similarity	NPC133060
0.5526	Remote Similarity	NPC470556
0.5488	Remote Similarity	NPC469933
0.5385	Remote Similarity	NPC474735
0.5316	Remote Similarity	NPC323137
0.5316	Remote Similarity	NPC249942
0.519	Remote Similarity	NPC290671
0.5128	Remote Similarity	NPC140120
0.5128	Remote Similarity	NPC78554
0.5125	Remote Similarity	NPC470554
0.5063	Remote Similarity	NPC321372

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC188632 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	1982
0.1-0.2	7046
0.2-0.3	122
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