NPASS Compound

Natural Product: NPC473649

Natural Product ID	NPC473649
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Calamistrin F
IUPAC Name	(2S)-4-[(15R)-3,15-dihydroxy-15-[(2R,5R)-5-[(2R,5R)-5-[(1S)-1-hydroxynonyl]oxolan-2-yl]oxolan-2-yl]pentadecyl]-2-methyl-2H-furan-5-one
Synonyms	Calamistrin F
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL448171
PubChem CID	44558949
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002518] Annonaceous acetogenins

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 110112 0 0 0 0 0 0 0 0999 V2000 12.6877 3.6278 1.9520 C 0 0 0 0 0 0 0 0 0 0 0 0 11.7711 2.5761 1.3951 C 0 0 0 0 0 0 0 0 0 0 0 0 11.8805 2.5920 -0.0916 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0103 1.5632 -0.7326 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5758 1.8223 -0.3916 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6383 0.8136 -1.0519 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8812 -0.5881 -0.6420 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0024 -1.6205 -1.1860 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5764 -1.7798 -0.7971 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6950 -0.6220 -1.0082 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4429 0.1375 0.3295 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2308 0.9561 -0.0904 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6955 0.1528 -1.2311 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3068 -1.0906 -1.0731 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2189 0.0782 -1.3369 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8739 -0.8150 -2.5070 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7210 -2.1557 -1.8713 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6217 -1.8469 -0.4067 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5744 -0.4731 -0.2389 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4349 -2.5844 0.1744 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4133 -2.5391 1.6782 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3311 -1.2386 2.3265 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7784 -0.3157 2.1456 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1478 -0.6458 2.5445 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8613 -1.7896 1.9586 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2624 -1.8079 2.6050 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0673 -2.9697 2.0909 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2500 -2.9062 0.6116 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9729 -1.6240 0.1818 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3206 -1.5910 0.7974 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1112 -0.3777 0.4538 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3790 -0.1745 -0.9959 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2164 1.0804 -1.1844 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.5464 1.0143 -0.4914 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 2.2977 -0.7904 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.4071 2.4081 -1.4085 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.7629 3.8294 -1.5055 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.7307 4.5222 -0.8747 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.7874 3.6247 -0.4305 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7059 3.9115 0.1806 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.7760 4.1687 -3.0085 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1507 0.1060 -1.6392 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7541 -2.1803 -0.4217 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1474 -2.7898 -1.7837 O 0 0 0 0 0 0 0 0 0 0 0 0 12.0811 4.4234 2.4089 H 0 0 0 0 0 0 0 0 0 0 0 0 13.2667 4.1118 1.1291 H 0 0 0 0 0 0 0 0 0 0 0 0 13.3751 3.1513 2.6899 H 0 0 0 0 0 0 0 0 0 0 0 0 12.1256 1.5789 1.7516 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7481 2.7616 1.7778 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5643 3.5917 -0.5132 H 0 0 0 0 0 0 0 0 0 0 0 0 12.9403 2.4415 -0.3846 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3335 0.5235 -0.4613 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1774 1.6235 -1.8456 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3050 2.8276 -0.7347 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4404 1.7177 0.7243 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6467 1.1995 -1.0393 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9868 0.8527 -2.1601 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8810 -0.6463 0.4912 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9766 -0.8192 -0.8732 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0379 -1.5772 -2.3480 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5509 -2.6175 -1.0351 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4568 -2.2956 0.1666 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8507 0.0024 -1.8520 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3071 0.6686 0.6192 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1375 -0.6724 1.0438 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5369 1.1012 0.7473 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6384 1.9106 -0.4877 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0823 0.5541 -2.1965 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8036 1.0758 -1.5328 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9453 -0.4647 -3.0006 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7237 -0.8565 -3.2066 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7390 -2.5842 -2.1985 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5589 -2.8482 -2.1056 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5777 -2.1863 0.0551 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5663 -3.6515 -0.1036 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2474 -3.3466 2.0389 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4513 -2.9592 1.9515 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4700 -1.3926 3.4415 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2825 -0.6649 2.0673 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5008 0.6137 2.7570 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7831 0.1511 1.1023 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8001 0.2678 2.3509 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2562 -0.7476 3.6747 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4757 -2.7882 2.1070 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0794 -1.5521 0.8798 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7646 -0.8377 2.4198 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1283 -1.9100 3.6873 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0328 -3.0460 2.6255 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5025 -3.8932 2.3975 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2925 -2.9254 0.0817 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9012 -3.7761 0.3137 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3364 -0.7670 0.4673 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0170 -1.6395 -0.9357 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8990 -2.4815 0.4332 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2987 -1.7264 1.9067 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6147 0.5711 0.8186 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0608 -0.4399 1.0537 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9007 -1.0140 -1.4792 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6693 1.9783 -0.8114 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3607 1.2631 -2.2837 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3723 0.9640 0.6082 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1446 0.1561 -0.8381 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.9751 1.5619 -1.7751 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.7579 4.0570 -1.0638 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.2522 3.3560 -3.5708 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.6872 4.2077 -3.3036 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.2773 5.1394 -3.1940 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3178 0.3195 -2.5968 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0176 -2.7619 -1.1499 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6738 -3.5912 -1.5500 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 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 2 0 37 41 1 0 32 42 1 0 20 43 1 0 9 44 1 0 14 10 1 0 19 15 1 0 39 35 1 0 1 45 1 0 1 46 1 0 1 47 1 0 2 48 1 0 2 49 1 0 3 50 1 0 3 51 1 0 4 52 1 0 4 53 1 0 5 54 1 0 5 55 1 0 6 56 1 0 6 57 1 0 7 58 1 0 7 59 1 0 8 60 1 0 8 61 1 0 9 62 1 0 10 63 1 0 11 64 1 0 11 65 1 0 12 66 1 0 12 67 1 0 13 68 1 0 15 69 1 0 16 70 1 0 16 71 1 0 17 72 1 0 17 73 1 0 18 74 1 0 20 75 1 0 21 76 1 0 21 77 1 0 22 78 1 0 22 79 1 0 23 80 1 0 23 81 1 0 24 82 1 0 24 83 1 0 25 84 1 0 25 85 1 0 26 86 1 0 26 87 1 0 27 88 1 0 27 89 1 0 28 90 1 0 28 91 1 0 29 92 1 0 29 93 1 0 30 94 1 0 30 95 1 0 31 96 1 0 31 97 1 0 32 98 1 0 33 99 1 0 33100 1 0 34101 1 0 34102 1 0 36103 1 0 37104 1 0 41105 1 0 41106 1 0 41107 1 0 42108 1 0 43109 1 0 44110 1 0 M END

Standard InCHIKey	ORSYGIAIOCQPJE-OKFJYEHJSA-N
Standard InCHI	InChI=1S/C37H66O7/c1-3-4-5-6-13-16-19-31(39)33-23-25-35(43-33)36-26-24-34(44-36)32(40)20-17-14-11-9-7-8-10-12-15-18-30(38)22-21-29-27-28(2)42-37(29)41/h27-28,30-36,38-40H,3-26H2,1-2H3/t28-,30?,31-,32+,33+,34+,35+,36+/m0/s1
SMILES	CCCCCCCCC(C1CCC(O1)C2CCC(O2)C(CCCCCCCCCCCC(CCC3=CC(OC3=O)C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	622.48	Volume:	679.097 ? Van der Waals volume.
Dense:	0.917	LogP:	7.002 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.458 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.866 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	25.0	Rigid Bonds:	16.0
TPSA:	105.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.07	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.781	Fsp³:	0.919
MCE-18:	42.817 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.627	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.039 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.459	Promiscuous compounds:	0.004

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.177	MDCK Permeability:	-4.758
Pgp-inhibitor:	0.0	Pgp-substrate:	0.485
PAMPA:	0.445 ? 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):	1.0
20% Bioavailability (F20%):	0.996	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.996
Plasma Protein Binding (PPB):	93.758%	Volume Distribution (VD):	0.584
Fu:	3.616% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.006
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.297
BSEP inhibitor:	0.372

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.169
CYP2C19-inhibitor:	0.996	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.053	CYP2D6-substrate:	0.785
CYP3A4-inhibitor:	0.591	CYP3A4-substrate:	0.043
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.834
HLM stability:	0.018 ? 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):

6.427

Half-life (T1/2):

1.111

ADMET: Toxicity

hERG Blockers:	0.823	hERG Blockers (10um):	0.939
Human Hepatotoxicity (H-HT):	0.506	Drug-induced Liver Injury (DILI):	0.022
AMES Toxicity:	0.036	Rat Oral Acute Toxicity:	0.063
Maximum Recommended Daily Dose:	0.659	Skin Sensitization:	0.999
Carcinogencity:	0.042	Eye Corrosion:	0.0
Eye Irritation:	0.029	Respiratory Toxicity:	0.761
Drug-induced Neurotoxicity:	0.024	Ototoxicity:	0.946
Hematotoxicity:	0.012	Drug-induced Nephrotoxicity:	0.589
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.085
A549 Cytotoxicity:	0.683	Hek293 Cytotoxicity:	0.467
BCF:	1.062 ? 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:	5.098 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.434 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.906 ? 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
NPO210	Uvaria calamistrata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10075755]
NPO210	Uvaria calamistrata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11000019]
NPO210	Uvaria calamistrata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO210	Uvaria calamistrata	Species	Annonaceae	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	3

Activity Type	# Activity
Cell line	2
Non-molecular	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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	0.0366	ug.mL-1	PMID[21090801]
NPT91	Cell line	KB	Homo sapiens	IC50	=	0.051	ug.mL-1	PMID[21090801]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	0.00227	ug.mL-1	PMID[11000019]

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 NPC473649 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	16691
0.1-0.2	29625
0.2-0.3	3199
0.3-0.4	110
0.4-0.5	28
0.5-0.6	35
0.6-0.7	56
0.7-0.8	0
0.8-0.85	34
0.85-0.9	12
0.9-0.95	4
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC154097
1.0	High Similarity	NPC159750
1.0	High Similarity	NPC73248
1.0	High Similarity	NPC470401
0.9773	High Similarity	NPC604764
0.9111	High Similarity	NPC473156
0.9111	High Similarity	NPC282815
0.9111	High Similarity	NPC600956
0.9111	High Similarity	NPC610454
0.8913	High Similarity	NPC473671
0.8913	High Similarity	NPC475268
0.8913	High Similarity	NPC470400
0.8913	High Similarity	NPC77871
0.8913	High Similarity	NPC9678
0.8913	High Similarity	NPC319036
0.8913	High Similarity	NPC605867
0.8864	High Similarity	NPC100921
0.8864	High Similarity	NPC477018
0.8776	High Similarity	NPC89001
0.8723	High Similarity	NPC132940
0.8542	High Similarity	NPC20533
0.8444	Intermediate Similarity	NPC25764
0.8444	Intermediate Similarity	NPC235809
0.8444	Intermediate Similarity	NPC39279
0.8444	Intermediate Similarity	NPC39167
0.8444	Intermediate Similarity	NPC292809
0.8444	Intermediate Similarity	NPC202055
0.8444	Intermediate Similarity	NPC606804
0.8444	Intermediate Similarity	NPC607425
0.8444	Intermediate Similarity	NPC608574
0.8298	Intermediate Similarity	NPC93794
0.8298	Intermediate Similarity	NPC473504
0.8298	Intermediate Similarity	NPC81778
0.8298	Intermediate Similarity	NPC40066
0.8298	Intermediate Similarity	NPC600524
0.8298	Intermediate Similarity	NPC608355
0.8085	Intermediate Similarity	NPC81045
0.8085	Intermediate Similarity	NPC39754
0.8085	Intermediate Similarity	NPC171135
0.8085	Intermediate Similarity	NPC61257
0.8085	Intermediate Similarity	NPC320569
0.8085	Intermediate Similarity	NPC133730
0.8085	Intermediate Similarity	NPC191929
0.8085	Intermediate Similarity	NPC100454
0.8085	Intermediate Similarity	NPC242364
0.8085	Intermediate Similarity	NPC172821
0.8085	Intermediate Similarity	NPC274446
0.8085	Intermediate Similarity	NPC485251
0.8085	Intermediate Similarity	NPC151403
0.8085	Intermediate Similarity	NPC261952
0.8085	Intermediate Similarity	NPC605171
0.8043	Intermediate Similarity	NPC475159
0.8043	Intermediate Similarity	NPC131002
0.8043	Intermediate Similarity	NPC473780
0.8043	Intermediate Similarity	NPC604521
0.7959	Intermediate Similarity	NPC42598
0.7843	Intermediate Similarity	NPC120398
0.7843	Intermediate Similarity	NPC471567
0.78	Intermediate Similarity	NPC309211
0.78	Intermediate Similarity	NPC477010
0.7755	Intermediate Similarity	NPC219652
0.7755	Intermediate Similarity	NPC473840
0.7708	Intermediate Similarity	NPC156804
0.7451	Intermediate Similarity	NPC485250
0.7451	Intermediate Similarity	NPC602738
0.7451	Intermediate Similarity	NPC605396
0.74	Intermediate Similarity	NPC25703
0.7391	Intermediate Similarity	NPC73310
0.7391	Intermediate Similarity	NPC473529
0.7391	Intermediate Similarity	NPC180363
0.7391	Intermediate Similarity	NPC94875
0.7391	Intermediate Similarity	NPC11332
0.7391	Intermediate Similarity	NPC145914
0.7391	Intermediate Similarity	NPC601174
0.7391	Intermediate Similarity	NPC601403
0.7391	Intermediate Similarity	NPC603568
0.7391	Intermediate Similarity	NPC604330
0.7391	Intermediate Similarity	NPC608300
0.7391	Intermediate Similarity	NPC611200
0.7391	Intermediate Similarity	NPC611571
0.7292	Intermediate Similarity	NPC107986
0.7292	Intermediate Similarity	NPC223871
0.7292	Intermediate Similarity	NPC231009
0.7292	Intermediate Similarity	NPC103284
0.7292	Intermediate Similarity	NPC110710
0.7292	Intermediate Similarity	NPC1083
0.7292	Intermediate Similarity	NPC82795
0.7292	Intermediate Similarity	NPC286338
0.7292	Intermediate Similarity	NPC603931
0.7292	Intermediate Similarity	NPC604237
0.72	Intermediate Similarity	NPC163093
0.717	Intermediate Similarity	NPC169511
0.717	Intermediate Similarity	NPC287164
0.717	Intermediate Similarity	NPC234077
0.717	Intermediate Similarity	NPC473995
0.7143	Intermediate Similarity	NPC488253
0.7143	Intermediate Similarity	NPC473669
0.7143	Intermediate Similarity	NPC488251
0.7115	Intermediate Similarity	NPC329838
0.7083	Intermediate Similarity	NPC606043
0.7	Intermediate Similarity	NPC232555
0.7	Intermediate Similarity	NPC171174
0.7	Intermediate Similarity	NPC114694
0.7	Intermediate Similarity	NPC485248
0.7	Intermediate Similarity	NPC142117
0.7	Intermediate Similarity	NPC480249
0.7	Intermediate Similarity	NPC485249
0.7	Intermediate Similarity	NPC240695
0.6939	Remote Similarity	NPC329829
0.6909	Remote Similarity	NPC239517
0.6863	Remote Similarity	NPC488632
0.6863	Remote Similarity	NPC477011
0.6852	Remote Similarity	NPC258068
0.6852	Remote Similarity	NPC476583
0.6786	Remote Similarity	NPC473520
0.6786	Remote Similarity	NPC91067
0.6727	Remote Similarity	NPC477014
0.6727	Remote Similarity	NPC477013
0.6667	Remote Similarity	NPC473905
0.6667	Remote Similarity	NPC182383
0.661	Remote Similarity	NPC477017
0.661	Remote Similarity	NPC477016
0.6604	Remote Similarity	NPC178215
0.6552	Remote Similarity	NPC473663
0.6552	Remote Similarity	NPC473723
0.6552	Remote Similarity	NPC475173
0.6538	Remote Similarity	NPC134865
0.6538	Remote Similarity	NPC103523
0.6538	Remote Similarity	NPC144415
0.6538	Remote Similarity	NPC488627
0.6538	Remote Similarity	NPC488631
0.6538	Remote Similarity	NPC607439
0.6538	Remote Similarity	NPC608157
0.6481	Remote Similarity	NPC488250
0.6415	Remote Similarity	NPC280621
0.6415	Remote Similarity	NPC48338
0.6415	Remote Similarity	NPC241360
0.6415	Remote Similarity	NPC293136
0.6415	Remote Similarity	NPC488628
0.6364	Remote Similarity	NPC69082
0.6364	Remote Similarity	NPC488249
0.6296	Remote Similarity	NPC473687
0.6296	Remote Similarity	NPC204686
0.6296	Remote Similarity	NPC219498
0.6296	Remote Similarity	NPC65930
0.6296	Remote Similarity	NPC308412
0.6296	Remote Similarity	NPC134885
0.6296	Remote Similarity	NPC488247
0.6296	Remote Similarity	NPC210218
0.6296	Remote Similarity	NPC488248
0.6226	Remote Similarity	NPC47937
0.6207	Remote Similarity	NPC280612
0.6182	Remote Similarity	NPC20621
0.6182	Remote Similarity	NPC318963
0.6182	Remote Similarity	NPC605101
0.617	Remote Similarity	NPC608138
0.614	Remote Similarity	NPC488623
0.614	Remote Similarity	NPC488624
0.614	Remote Similarity	NPC488629
0.6111	Remote Similarity	NPC480079
0.6071	Remote Similarity	NPC473478
0.6071	Remote Similarity	NPC473651
0.6071	Remote Similarity	NPC66346
0.6071	Remote Similarity	NPC477012
0.5965	Remote Similarity	NPC283085
0.5965	Remote Similarity	NPC130359
0.5965	Remote Similarity	NPC14901
0.5893	Remote Similarity	NPC329615
0.5893	Remote Similarity	NPC134807
0.5882	Remote Similarity	NPC112685
0.5833	Remote Similarity	NPC609415
0.5789	Remote Similarity	NPC473707
0.5789	Remote Similarity	NPC20339
0.5769	Remote Similarity	NPC480072
0.569	Remote Similarity	NPC231096
0.569	Remote Similarity	NPC475581
0.569	Remote Similarity	NPC62118
0.569	Remote Similarity	NPC132496
0.569	Remote Similarity	NPC107717
0.569	Remote Similarity	NPC488252
0.5667	Remote Similarity	NPC488630
0.5667	Remote Similarity	NPC488625
0.5667	Remote Similarity	NPC488626
0.5593	Remote Similarity	NPC233551
0.5593	Remote Similarity	NPC40376
0.5593	Remote Similarity	NPC480082
0.5593	Remote Similarity	NPC21208
0.5574	Remote Similarity	NPC253801
0.5574	Remote Similarity	NPC477015
0.5517	Remote Similarity	NPC480076
0.5517	Remote Similarity	NPC480077
0.5424	Remote Similarity	NPC606740
0.5424	Remote Similarity	NPC608614
0.541	Remote Similarity	NPC480081
0.5333	Remote Similarity	NPC320458
0.5254	Remote Similarity	NPC139418
0.5185	Remote Similarity	NPC228411
0.5161	Remote Similarity	NPC322529
0.5088	Remote Similarity	NPC480078

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473649 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6443
0.1-0.2	2642
0.2-0.3	65
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