NPASS Compound

Natural Product: NPC475159

Natural Product ID	NPC475159
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Calamistrin D
IUPAC Name	(2S)-4-[(17R)-11,17-dihydroxy-17-[(2R,5R)-5-[(1S)-1-hydroxyundecyl]oxolan-2-yl]heptadecyl]-2-methyl-2H-furan-5-one
Synonyms	Calamistrin D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL499675
PubChem CID	10371515
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 111112 0 0 0 0 0 0 0 0999 V2000 -13.6885 0.4861 -1.8269 C 0 0 0 0 0 0 0 0 0 0 0 0 -14.6800 0.0472 -0.7411 C 0 0 0 0 0 0 0 0 0 0 0 0 -14.0040 0.2849 0.5755 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.6941 -0.5738 0.6076 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.0289 -0.3279 1.9072 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.8160 -1.0370 2.2970 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5529 -0.9749 1.5664 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5330 -1.5201 0.1892 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1158 -1.3920 -0.3965 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0876 -2.1019 0.4184 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7049 -1.9889 -0.2133 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3085 -0.5715 -0.3372 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3003 0.2391 0.9295 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5962 1.4995 0.4014 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7269 0.9413 -0.6766 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0059 -0.4127 -0.8250 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2527 1.1073 -0.3974 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7825 0.3959 0.8078 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3077 0.6447 1.0309 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6032 0.1988 -0.0387 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0600 0.4687 0.4046 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3716 1.8890 0.6184 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7049 2.3219 1.0381 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9021 2.1129 0.2131 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3084 0.7318 -0.1636 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6782 0.7409 -0.8837 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6592 1.5223 -2.1223 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9372 1.5446 -2.8650 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0839 2.2347 -2.2664 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6290 1.8272 -0.9681 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0923 0.3790 -0.8591 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5939 0.2215 0.5382 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0506 -1.1101 0.9381 C 0 0 0 0 0 0 0 0 0 0 0 0 12.1471 -1.7589 0.2159 C 0 0 0 0 0 0 0 0 0 0 0 0 13.3064 -2.0296 0.8408 C 0 0 0 0 0 0 0 0 0 0 0 0 14.2400 -2.6778 -0.0940 C 0 0 0 0 0 0 0 0 0 0 0 0 13.5216 -2.8506 -1.2829 O 0 0 0 0 0 0 0 0 0 0 0 0 12.2703 -2.2756 -1.1267 C 0 0 0 0 0 0 0 0 0 0 0 0 11.3707 -2.2192 -2.0353 O 0 0 0 0 0 0 0 0 0 0 0 0 14.7529 -3.9965 0.4543 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6151 3.7524 1.2130 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6171 0.5245 -1.5236 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8652 -2.7274 0.6288 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.1015 1.3465 -1.4015 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.2937 0.8338 -2.6912 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.0534 -0.3539 -2.1303 H 0 0 0 0 0 0 0 0 0 0 0 0 -15.5362 0.7352 -0.8167 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.9500 -1.0010 -0.9317 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.6338 0.0428 1.4303 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.6563 1.3261 0.6234 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.9489 -1.6309 0.4320 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.1077 -0.1222 -0.2389 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8775 0.8108 1.9906 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.8131 -0.4927 2.7257 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0926 -2.1623 2.3463 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5365 -0.7836 3.3995 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1342 0.0922 1.5811 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8085 -1.6010 2.1842 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8432 -2.5847 0.2049 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1716 -0.9592 -0.4784 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9550 -0.2950 -0.4648 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1846 -1.7945 -1.4193 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3197 -3.1704 0.5057 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9649 -1.6299 1.4285 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7570 -2.4346 -1.2056 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0387 -0.0719 -1.0240 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6813 -0.2545 1.7061 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3017 0.4933 1.3095 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0653 2.0213 1.2115 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3726 2.1695 -0.0154 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9576 1.4416 -1.6369 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9301 2.1571 -0.3958 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9108 -0.7074 0.7615 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2810 0.7054 1.7505 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1632 1.7659 1.1689 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0365 0.2288 2.0047 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5336 0.8320 -0.9771 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5092 -0.8672 -0.2831 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7414 -0.1214 -0.1845 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1092 -0.0164 1.4491 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1111 2.4389 -0.3539 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5878 2.3416 1.3234 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9747 1.9120 2.0763 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7422 2.7274 -0.7435 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8143 2.5934 0.6768 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6055 0.4320 -1.0136 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2844 -0.0278 0.5901 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4022 0.9645 -0.1057 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8328 -0.3565 -1.1151 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3001 2.5947 -1.9374 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8536 1.0987 -2.8047 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2922 0.4831 -3.1016 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7711 1.9736 -3.9091 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8507 3.3652 -2.1450 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9577 2.2522 -3.0115 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1313 2.2284 -0.0972 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6570 2.4039 -0.9073 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3439 -0.3602 -1.0923 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9227 0.2889 -1.6120 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7321 0.5515 1.2131 H 0 0 0 0 0 0 0 0 0 0 0 0 11.3559 1.0322 0.7393 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2402 -1.0806 2.0495 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1672 -1.8301 0.8357 H 0 0 0 0 0 0 0 0 0 0 0 0 13.5674 -1.8231 1.8703 H 0 0 0 0 0 0 0 0 0 0 0 0 15.1205 -1.9983 -0.2266 H 0 0 0 0 0 0 0 0 0 0 0 0 15.8253 -3.9197 0.7638 H 0 0 0 0 0 0 0 0 0 0 0 0 14.6975 -4.7757 -0.3279 H 0 0 0 0 0 0 0 0 0 0 0 0 14.1757 -4.2679 1.3393 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8074 3.8740 1.8095 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8618 1.0481 -2.3263 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9805 -3.6820 0.3235 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 14 15 1 0 15 16 1 0 15 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 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 2 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 2 0 36 40 1 0 23 41 1 0 17 42 1 0 11 43 1 0 16 12 1 0 38 34 1 0 1 44 1 0 1 45 1 0 1 46 1 0 2 47 1 0 2 48 1 0 3 49 1 0 3 50 1 0 4 51 1 0 4 52 1 0 5 53 1 0 5 54 1 0 6 55 1 0 6 56 1 0 7 57 1 0 7 58 1 0 8 59 1 0 8 60 1 0 9 61 1 0 9 62 1 0 10 63 1 0 10 64 1 0 11 65 1 0 12 66 1 0 13 67 1 0 13 68 1 0 14 69 1 0 14 70 1 0 15 71 1 0 17 72 1 0 18 73 1 0 18 74 1 0 19 75 1 0 19 76 1 0 20 77 1 0 20 78 1 0 21 79 1 0 21 80 1 0 22 81 1 0 22 82 1 0 23 83 1 0 24 84 1 0 24 85 1 0 25 86 1 0 25 87 1 0 26 88 1 0 26 89 1 0 27 90 1 0 27 91 1 0 28 92 1 0 28 93 1 0 29 94 1 0 29 95 1 0 30 96 1 0 30 97 1 0 31 98 1 0 31 99 1 0 32100 1 0 32101 1 0 33102 1 0 33103 1 0 35104 1 0 36105 1 0 40106 1 0 40107 1 0 40108 1 0 41109 1 0 42110 1 0 43111 1 0 M END

Standard InCHIKey	JOHOCUBTTQAHLI-NWGXSNPTSA-N
Standard InCHI	InChI=1S/C37H68O6/c1-3-4-5-6-7-12-15-20-25-33(39)35-27-28-36(43-35)34(40)26-21-16-19-24-32(38)23-18-14-11-9-8-10-13-17-22-31-29-30(2)42-37(31)41/h29-30,32-36,38-40H,3-28H2,1-2H3/t30-,32?,33-,34+,35+,36+/m0/s1
SMILES	CCCCCCCCCCC(C1CCC(O1)C(CCCCCC(CCCCCCCCCCC2=CC(OC2=O)C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	608.5	Volume:	678.863 ? Van der Waals volume.
Dense:	0.896	LogP:	8.13 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.611 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.413 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	28.0	Rigid Bonds:	11.0
TPSA:	96.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.061	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.445	Fsp³:	0.919
MCE-18:	29.972 ? 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:	0.652	Fluc inhibitor:	0.025 ? 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:	0.035 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.452	Promiscuous compounds:	0.006

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.22	MDCK Permeability:	-4.844
Pgp-inhibitor:	0.001	Pgp-substrate:	0.194
PAMPA:	0.055 ? 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%):	0.995	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.992
Plasma Protein Binding (PPB):	95.946%	Volume Distribution (VD):	0.61
Fu:	2.748% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.002
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.371
BSEP inhibitor:	0.664

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.857
CYP2C19-inhibitor:	0.461	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.035
CYP2D6-inhibitor:	0.922	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.966
HLM stability:	0.025 ? 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):

5.855

Half-life (T1/2):

1.395

ADMET: Toxicity

hERG Blockers:	0.753	hERG Blockers (10um):	0.946
Human Hepatotoxicity (H-HT):	0.562	Drug-induced Liver Injury (DILI):	0.043
AMES Toxicity:	0.029	Rat Oral Acute Toxicity:	0.043
Maximum Recommended Daily Dose:	0.61	Skin Sensitization:	1.0
Carcinogencity:	0.053	Eye Corrosion:	0.0
Eye Irritation:	0.218	Respiratory Toxicity:	0.76
Drug-induced Neurotoxicity:	0.013	Ototoxicity:	0.924
Hematotoxicity:	0.019	Drug-induced Nephrotoxicity:	0.673
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.066
A549 Cytotoxicity:	0.696	Hek293 Cytotoxicity:	0.317
BCF:	0.66 ? 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:	5.086 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.634 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.753 ? 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	=	0.431	ug.mL-1	Open TG-GATES in vivo data: Biochemistry
NPT91	Cell line	KB	Homo sapiens	IC50	=	0.0273	ug.mL-1	Open TG-GATES in vivo data: Biochemistry
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	0.0732	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 NPC475159 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	15375
0.1-0.2	30198
0.2-0.3	3890
0.3-0.4	149
0.4-0.5	31
0.5-0.6	19
0.6-0.7	45
0.7-0.8	0
0.8-0.85	37
0.85-0.9	13
0.9-0.95	15
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC131002
1.0	High Similarity	NPC473780
1.0	High Similarity	NPC604521
0.9524	High Similarity	NPC156804
0.925	High Similarity	NPC73310
0.925	High Similarity	NPC473529
0.925	High Similarity	NPC180363
0.925	High Similarity	NPC94875
0.925	High Similarity	NPC11332
0.925	High Similarity	NPC145914
0.925	High Similarity	NPC601174
0.925	High Similarity	NPC601403
0.925	High Similarity	NPC603568
0.925	High Similarity	NPC604330
0.925	High Similarity	NPC608300
0.925	High Similarity	NPC611200
0.925	High Similarity	NPC611571
0.9048	High Similarity	NPC100921
0.9048	High Similarity	NPC477018
0.8864	High Similarity	NPC473156
0.8864	High Similarity	NPC163093
0.8864	High Similarity	NPC282815
0.8864	High Similarity	NPC600956
0.8696	High Similarity	NPC329838
0.8667	High Similarity	NPC473671
0.8667	High Similarity	NPC475268
0.8667	High Similarity	NPC470400
0.8667	High Similarity	NPC77871
0.8667	High Similarity	NPC9678
0.8667	High Similarity	NPC319036
0.8667	High Similarity	NPC605867
0.8605	High Similarity	NPC329829
0.8478	Intermediate Similarity	NPC132940
0.8444	Intermediate Similarity	NPC610454
0.8333	Intermediate Similarity	NPC258068
0.8333	Intermediate Similarity	NPC476583
0.8298	Intermediate Similarity	NPC20533
0.8182	Intermediate Similarity	NPC107986
0.8182	Intermediate Similarity	NPC25764
0.8182	Intermediate Similarity	NPC235809
0.8182	Intermediate Similarity	NPC223871
0.8182	Intermediate Similarity	NPC231009
0.8182	Intermediate Similarity	NPC103284
0.8182	Intermediate Similarity	NPC110710
0.8182	Intermediate Similarity	NPC39279
0.8182	Intermediate Similarity	NPC1083
0.8182	Intermediate Similarity	NPC39167
0.8182	Intermediate Similarity	NPC82795
0.8182	Intermediate Similarity	NPC292809
0.8182	Intermediate Similarity	NPC286338
0.8182	Intermediate Similarity	NPC202055
0.8182	Intermediate Similarity	NPC603931
0.8182	Intermediate Similarity	NPC604237
0.8182	Intermediate Similarity	NPC606804
0.8182	Intermediate Similarity	NPC607425
0.8182	Intermediate Similarity	NPC608574
0.8163	Intermediate Similarity	NPC477014
0.8163	Intermediate Similarity	NPC477013
0.8043	Intermediate Similarity	NPC473649
0.8043	Intermediate Similarity	NPC154097
0.8043	Intermediate Similarity	NPC144415
0.8043	Intermediate Similarity	NPC159750
0.8043	Intermediate Similarity	NPC73248
0.8043	Intermediate Similarity	NPC470401
0.8043	Intermediate Similarity	NPC607439
0.8043	Intermediate Similarity	NPC608157
0.8	Intermediate Similarity	NPC488253
0.8	Intermediate Similarity	NPC473669
0.8	Intermediate Similarity	NPC488251
0.7955	Intermediate Similarity	NPC606043
0.7917	Intermediate Similarity	NPC309211
0.7917	Intermediate Similarity	NPC477010
0.7872	Intermediate Similarity	NPC241360
0.7872	Intermediate Similarity	NPC293136
0.7872	Intermediate Similarity	NPC604764
0.7826	Intermediate Similarity	NPC232555
0.7826	Intermediate Similarity	NPC171174
0.7826	Intermediate Similarity	NPC114694
0.7826	Intermediate Similarity	NPC485248
0.7826	Intermediate Similarity	NPC142117
0.7826	Intermediate Similarity	NPC480249
0.7826	Intermediate Similarity	NPC485249
0.7826	Intermediate Similarity	NPC240695
0.766	Intermediate Similarity	NPC488632
0.766	Intermediate Similarity	NPC477011
0.76	Intermediate Similarity	NPC120398
0.76	Intermediate Similarity	NPC471567
0.75	Intermediate Similarity	NPC219652
0.75	Intermediate Similarity	NPC473840
0.75	Intermediate Similarity	NPC280612
0.7447	Intermediate Similarity	NPC182383
0.7347	Intermediate Similarity	NPC178215
0.7347	Intermediate Similarity	NPC65930
0.7292	Intermediate Similarity	NPC93794
0.7292	Intermediate Similarity	NPC134865
0.7292	Intermediate Similarity	NPC473504
0.7292	Intermediate Similarity	NPC103523
0.7292	Intermediate Similarity	NPC81778
0.7292	Intermediate Similarity	NPC40066
0.7292	Intermediate Similarity	NPC488627
0.7292	Intermediate Similarity	NPC488631
0.72	Intermediate Similarity	NPC485250
0.72	Intermediate Similarity	NPC488250
0.72	Intermediate Similarity	NPC605396
0.7143	Intermediate Similarity	NPC280621
0.7143	Intermediate Similarity	NPC25703
0.7143	Intermediate Similarity	NPC48338
0.7143	Intermediate Similarity	NPC488628
0.7115	Intermediate Similarity	NPC89001
0.7083	Intermediate Similarity	NPC81045
0.7083	Intermediate Similarity	NPC39754
0.7083	Intermediate Similarity	NPC171135
0.7083	Intermediate Similarity	NPC61257
0.7083	Intermediate Similarity	NPC320569
0.7083	Intermediate Similarity	NPC133730
0.7083	Intermediate Similarity	NPC191929
0.7083	Intermediate Similarity	NPC100454
0.7083	Intermediate Similarity	NPC242364
0.7083	Intermediate Similarity	NPC172821
0.7083	Intermediate Similarity	NPC274446
0.7083	Intermediate Similarity	NPC485251
0.7083	Intermediate Similarity	NPC151403
0.7083	Intermediate Similarity	NPC261952
0.7083	Intermediate Similarity	NPC605171
0.7059	Intermediate Similarity	NPC69082
0.7059	Intermediate Similarity	NPC488249
0.7	Intermediate Similarity	NPC42598
0.7	Intermediate Similarity	NPC473687
0.7	Intermediate Similarity	NPC204686
0.7	Intermediate Similarity	NPC219498
0.7	Intermediate Similarity	NPC308412
0.7	Intermediate Similarity	NPC134885
0.7	Intermediate Similarity	NPC488247
0.7	Intermediate Similarity	NPC210218
0.7	Intermediate Similarity	NPC488248
0.6977	Remote Similarity	NPC609415
0.6939	Remote Similarity	NPC47937
0.6939	Remote Similarity	NPC600524
0.6939	Remote Similarity	NPC608355
0.6923	Remote Similarity	NPC473995
0.6863	Remote Similarity	NPC329615
0.6863	Remote Similarity	NPC20621
0.6863	Remote Similarity	NPC318963
0.6863	Remote Similarity	NPC605101
0.6731	Remote Similarity	NPC477012
0.6727	Remote Similarity	NPC477015
0.6667	Remote Similarity	NPC477017
0.6667	Remote Similarity	NPC477016
0.6604	Remote Similarity	NPC130359
0.6604	Remote Similarity	NPC14901
0.6591	Remote Similarity	NPC608138
0.6545	Remote Similarity	NPC473520
0.6538	Remote Similarity	NPC134807
0.6538	Remote Similarity	NPC602738
0.6481	Remote Similarity	NPC488623
0.6481	Remote Similarity	NPC320458
0.6481	Remote Similarity	NPC488624
0.6481	Remote Similarity	NPC480082
0.6481	Remote Similarity	NPC488629
0.6429	Remote Similarity	NPC473905
0.6429	Remote Similarity	NPC253801
0.6415	Remote Similarity	NPC473478
0.6415	Remote Similarity	NPC473651
0.6415	Remote Similarity	NPC66346
0.6296	Remote Similarity	NPC283085
0.6296	Remote Similarity	NPC169511
0.6296	Remote Similarity	NPC287164
0.6296	Remote Similarity	NPC234077
0.625	Remote Similarity	NPC488630
0.625	Remote Similarity	NPC112685
0.625	Remote Similarity	NPC488625
0.625	Remote Similarity	NPC488626
0.6111	Remote Similarity	NPC20339
0.6071	Remote Similarity	NPC239517
0.6	Remote Similarity	NPC231096
0.6	Remote Similarity	NPC475581
0.6	Remote Similarity	NPC62118
0.6	Remote Similarity	NPC132496
0.6	Remote Similarity	NPC107717
0.6	Remote Similarity	NPC488252
0.5965	Remote Similarity	NPC322529
0.5965	Remote Similarity	NPC91067
0.5893	Remote Similarity	NPC233551
0.5893	Remote Similarity	NPC40376
0.5893	Remote Similarity	NPC21208
0.5818	Remote Similarity	NPC139418
0.5763	Remote Similarity	NPC473663
0.5763	Remote Similarity	NPC473723
0.5763	Remote Similarity	NPC475173
0.575	Remote Similarity	NPC84038
0.5741	Remote Similarity	NPC478998
0.5714	Remote Similarity	NPC606740
0.5714	Remote Similarity	NPC608614
0.569	Remote Similarity	NPC480081
0.5556	Remote Similarity	NPC480079
0.5472	Remote Similarity	NPC488234
0.5455	Remote Similarity	NPC473904
0.537	Remote Similarity	NPC482767
0.537	Remote Similarity	NPC488246

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475159 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6234
0.1-0.2	2828
0.2-0.3	87
0.3-0.4	1
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