NPASS Compound

Natural Product: NPC203614

Natural Product ID	NPC203614
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cheatoglobosin D
IUPAC Name	n.a.
Synonyms	Cheatoglobosin D
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL520561
PubChem CID	23259920
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001819] Isoindoles and derivatives [CHEMONTID:0002496] Isoindolines [CHEMONTID:0001820] Isoindolones

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 75 79 0 0 0 0 0 0 0 0999 V2000 4.3453 1.2928 -1.5715 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6693 0.0927 -0.7334 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8004 0.4376 0.6918 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5210 0.9789 1.3158 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3840 1.1357 0.6975 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0891 1.6300 1.1458 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8096 3.0304 1.1766 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5921 3.7115 2.1094 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6212 3.2447 1.6432 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1339 4.4633 1.6614 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3342 2.0238 2.0528 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3259 1.0199 0.9123 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0192 0.8323 0.3124 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0895 1.3522 -1.0107 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2585 1.7573 -1.2825 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.1652 1.5939 -0.2048 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4629 0.9643 -0.4698 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5551 -0.4144 -0.8650 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6123 -1.3277 -1.2007 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1740 -2.5300 -1.5308 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.5016 -2.3668 -1.3997 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7848 -1.0875 -0.9936 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1007 -0.7221 -0.8097 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1416 -1.6191 -1.0266 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8331 -2.9088 -1.4371 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5220 -3.2864 -1.6240 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9088 1.4886 -2.0228 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5600 -0.4931 0.4410 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5030 -0.9926 1.6900 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2128 -1.3850 -0.4505 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3955 -1.5008 -1.7300 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2395 -2.6247 -2.2827 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3005 -2.8459 -3.4704 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0341 -3.4309 -1.2948 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7772 -2.2801 -0.4912 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0465 -1.1645 -1.1209 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2215 -2.6627 0.8542 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3200 -4.1018 -0.3649 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7244 2.3522 2.5240 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1143 2.2132 -0.9795 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5827 1.1082 -2.3537 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2512 1.6312 -2.1818 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8102 -0.1274 -1.0257 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2050 -0.3217 1.3667 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5595 1.2830 0.7466 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5863 1.2502 2.3629 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3849 0.8092 -0.3719 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9672 1.1992 2.1872 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9659 3.5863 0.2197 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4976 3.3602 3.0234 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5157 5.2890 1.3391 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1380 4.6815 1.9822 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8324 1.5514 2.9097 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8348 0.1194 1.2802 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3716 2.7261 0.0746 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9886 1.5849 -1.2620 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0879 1.0648 0.4834 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5380 -1.2282 -1.2491 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6837 -3.3987 -1.8240 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3234 0.2995 -0.4848 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1567 -1.3088 -0.8761 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6740 -3.5812 -1.5994 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3289 -4.2956 -1.9418 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6820 1.4484 -2.9939 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6406 -2.2666 0.1487 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9943 -0.9034 -2.5222 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7516 -4.0300 -1.8051 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7389 -1.1655 -2.2142 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6978 -2.1071 1.6621 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3311 -2.6511 0.9473 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9617 -3.7492 1.0517 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6184 -5.0612 -0.3741 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3208 1.4533 2.7472 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6186 2.8943 3.4917 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2980 2.9852 1.8582 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 5 6 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 6 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 14 27 1 0 13 28 1 0 28 29 2 0 28 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 32 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 34 38 1 0 11 39 1 0 36 2 1 0 13 6 1 0 22 18 1 0 16 12 1 0 26 21 1 0 1 40 1 0 1 41 1 0 1 42 1 0 2 43 1 6 3 44 1 0 3 45 1 0 4 46 1 0 5 47 1 0 6 48 1 1 7 49 1 6 8 50 1 0 10 51 1 0 10 52 1 0 11 53 1 1 12 54 1 1 16 55 1 1 17 56 1 0 17 57 1 0 19 58 1 0 20 59 1 0 23 60 1 0 24 61 1 0 25 62 1 0 26 63 1 0 27 64 1 0 30 65 1 0 31 66 1 0 34 67 1 6 36 68 1 0 37 69 1 0 37 70 1 0 37 71 1 0 38 72 1 0 39 73 1 0 39 74 1 0 39 75 1 0 M END

Standard InCHIKey	FTBNYQWFSWKCKW-WHHLLCSSSA-N
Standard InCHI	InChI=1S/C32H36N2O5/c1-17-8-7-10-23-30(38)20(4)19(3)28-25(15-21-16-33-24-11-6-5-9-22(21)24)34-31(39)32(23,28)27(36)13-12-26(35)29(37)18(2)14-17/h5-7,9-14,16-17,19,23,25,28-30,33,37-38H,4,8,15H2,1-3H3,(H,34,39)/b10-7+,13-12+,18-14+/t17-,19+,23-,25-,28-,29+,30+,32+/m0/s1
SMILES	C[C@H]1C/C=C/[C@H]2[C@H](O)C(=C)[C@H]([C@@H]3[C@]2(C(=N[C@H]3Cc2c[nH]c3c2cccc3)O)C(=O)/C=C/C(=O)[C@@H](/C(=C/1)/C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	528.26	Volume:	556.189 ? Van der Waals volume.
Dense:	0.95	LogP:	3.073 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.036 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.421 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	35.0
TPSA:	122.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	5.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.43	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.181	Fsp³:	0.406
MCE-18:	145.2 ? 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:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.839	Fluc inhibitor:	0.499 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.137 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.384 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.013	Promiscuous compounds:	0.524

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.458	MDCK Permeability:	-4.976
Pgp-inhibitor:	0.018	Pgp-substrate:	0.994
PAMPA:	0.997 ? 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):	0.003
20% Bioavailability (F20%):	0.883	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.515
Plasma Protein Binding (PPB):	93.274%	Volume Distribution (VD):	-0.036
Fu:	6.028% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.002
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.83
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.677
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.202
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.877
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.934
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.944 ? 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):

6.662

Half-life (T1/2):

0.931

ADMET: Toxicity

hERG Blockers:	0.003	hERG Blockers (10um):	0.009
Human Hepatotoxicity (H-HT):	0.999	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.616	Rat Oral Acute Toxicity:	0.711
Maximum Recommended Daily Dose:	0.391	Skin Sensitization:	1.0
Carcinogencity:	0.913	Eye Corrosion:	0.0
Eye Irritation:	0.919	Respiratory Toxicity:	0.954
Drug-induced Neurotoxicity:	0.259	Ototoxicity:	0.734
Hematotoxicity:	0.618	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.086
A549 Cytotoxicity:	0.422	Hek293 Cytotoxicity:	0.52
BCF:	1.3 ? 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:	4.067 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.727 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.15 ? 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
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12357398]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12483566]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15497948]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15921417]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16209910]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16499339]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16872138]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16904330]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17125234]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17827664]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19246197]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	Ginkgo biloba	n.a.	n.a.	PMID[19246197]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19427327]
NPO30621	Chaetomium brasiliense	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19663417]
NPO30621	Chaetomium brasiliense	Species	Chaetomiaceae	Eukaryota	n.a.	Doi Inthanon, Jomtong District, Chiangmai Province, Thailand	2006-JUN	PMID[19663417]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20225834]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20814854]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	mycelium	n.a.	PMID[21548578]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	isolated from the leaves of Viguiera robusta	n.a.	n.a.	PMID[21548578]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21548578]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21640594]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21854043]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22112725]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22593034]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23072467]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	Xichang of Sichuan Province, China	n.a.	PMID[26125976]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26343828]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[5066072]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7116505]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[CiteXplore Id]
NPO30621	Chaetomium brasiliense	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[CiteXplore Id]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30621	Chaetomium brasiliense	Species	Chaetomiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24171	Chaetomium globosum	Species	Chaetomiaceae	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	2
IZ	1

Activity Type	# Activity
Cell line	2
Organism	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
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	3.2	ug.mL-1	PMID[15497948]
NPT168	Cell line	P388	Mus musculus	IC50	=	4.92	ug.mL-1	PMID[15497948]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	3.0	mm	PMID[15497948]

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 NPC203614 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	11737
0.1-0.2	36515
0.2-0.3	1370
0.3-0.4	192
0.4-0.5	16
0.5-0.6	8
0.6-0.7	12
0.7-0.8	0
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8462	Intermediate Similarity	NPC87856
0.837	Intermediate Similarity	NPC204491
0.8261	Intermediate Similarity	NPC141428
0.8191	Intermediate Similarity	NPC235885
0.8152	Intermediate Similarity	NPC225821
0.7979	Intermediate Similarity	NPC487663
0.7449	Intermediate Similarity	NPC57690
0.7071	Intermediate Similarity	NPC151976
0.6939	Remote Similarity	NPC98715
0.6931	Remote Similarity	NPC2395
0.68	Remote Similarity	NPC46225
0.6569	Remote Similarity	NPC147446
0.6566	Remote Similarity	NPC267965
0.6465	Remote Similarity	NPC195239
0.6429	Remote Similarity	NPC157828
0.6373	Remote Similarity	NPC132211
0.6311	Remote Similarity	NPC487664
0.6154	Remote Similarity	NPC258062
0.6117	Remote Similarity	NPC487662
0.6019	Remote Similarity	NPC271862
0.5905	Remote Similarity	NPC487661
0.5596	Remote Similarity	NPC267926
0.5514	Remote Similarity	NPC266192
0.5505	Remote Similarity	NPC487657
0.5405	Remote Similarity	NPC487658
0.5268	Remote Similarity	NPC487660
0.5089	Remote Similarity	NPC127677
0.5043	Remote Similarity	NPC487659

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC203614 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3479
0.1-0.2	5463
0.2-0.3	175
0.3-0.4	33
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